Drug Information

General Information of This Drug
Drug ID DRG00019
Drug Name Methotrexate
Synonyms
methotrexate; 59-05-2; Rheumatrex; Amethopterin; Methylaminopterin; Metatrexan; Hdmtx; Abitrexate; Trexall; Mexate; Ledertrexate; Methylaminopterinum; (S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)pentanedioic acid; Methotrexatum; Antifolan; MTX; 4-Amino-10-methylfolic acid; Amethopterine; Metotrexato; Emtexate; Maxtrex; Rasuvo; Methotrexate hydrate; A-Methopterin; L-Amethopterin; A-Methpterin; Amethopterin L-; Folex-Pfs; Methotrexat-Ebewe; NSC-740; Methotrexate, L-; N-Bismethylpteroylglutamic acid; Farmitrexat; Medsatrexate; Methoblastin; Methotextrate; Methotrexat; Metotressato; Brimexate; Emthexat; Emthexate; Fauldexato; Lantarel; Lumexon; Metrotex; Novatrex; Otrexup; Tremetex; Trexeron; Trixilem; Texate; Metex; Mexate-Aq; alpha-Methopterin; CL-14377; Folex; NCI-C04671; JYLAMVO; Methotrexate Lpf; CCRIS 1109; Nordimet; Xatmep; EMT 25,299; 133073-73-1; 4-Aminomethylpteroylglutamic acid; HSDB 3123; NSC 740; CL 14377; UNII-YL5FZ2Y5U1; Methotrexatum [INN-Latin]; Metotrexato [INN-Spanish]; EINECS 200-413-8; YL5FZ2Y5U1; R 9985; REDITREX; NSC740; DTXSID4020822; CHEBI:44185; AI3-25299; TCMDC-125858; X 133; 4-Amino-N(sup 10)-methylpteroylglutamic acid; ADX-2191; MPI-2505; WR-19039; CHEMBL34259; DTXCID80822; (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid; R-9985; Kyselina 4-amino-N(sup 10)-methylpteroylglutamova; N-(p-(((2,4-Diamino-6-pteridyl)methyl)methylamino)benzoyl)glutamic acid; L-(+)-N-(p-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)glutamic acid; N-(4-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)-L-glutamicacid; N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid; N-(p-(((2,4-Diamino-6-pteridinyl)methyl)methylamino)benzoyl)-L-(+)-glutamic acid; N-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)carbonyl]-L-glutamic acid; Methotrexate [USAN:USP:INN:BAN:JAN]; NCGC00025060-04; 4-amino-N(10)-methylpteroylglutamic acid; MFCD00150847; Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)methylamino)benzoyl)-L-glutamova; METHOTREXATE (IARC); METHOTREXATE [IARC]; Methotrexatum (INN-Latin); Metotrexato (INN-Spanish); (2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid; Glutamic acid, N-(p-(((2,4-diamino-6-pteridinyl)methyl)methylamino)benzoyl)-, L-; METHOTREXATE (MART.); METHOTREXATE [MART.]; METHOTREXATE (USP-RS); METHOTREXATE [USP-RS]; Metotressato [DCIT]; Methotrexate, d-; METHOTREXATE (EP MONOGRAPH); METHOTREXATE (USP IMPURITY); METHOTREXATE [EP MONOGRAPH]; METHOTREXATE [USP IMPURITY]; METHOTREXATE (USP MONOGRAPH); METHOTREXATE [USP MONOGRAPH]; MLS001401431; [3H]methotrexate; Methotrexate (hydrate); Methotrexate (USAN:USP:INN:BAN:JAN); SMR000112001; [3H]-methotrexate; folic acid antagonist; 4-Amino-10-methylfolic acid hydrate; SR-01000075682; SMR000449324; Methotrexate (1.0mg/mL in Methanol with 0.1N NaOH); TCMDC-125488; Metolate; Antifolan hydrate; Intradose-MTX; MTX hydrate; 1dhi; 1dhj; 2drc; 4ocx; (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid; CAS-59-05-2; Prestwick_322; Otrexup (TN); Xatmep (TN); L-METHOTREXATE; OTREXUP PFS; Kyselina 4-amino-N(sup 10)-methylpteroylglutamova [Czech]; Methylaminopterin; MTX; DL-Amethopterin hydrate; Spectrum_001836; Tocris-1230; 4kn0; Methylaminopterin hydrate; Prestwick0_000135; Prestwick1_000135; Prestwick2_000135; Spectrum2_001077; Spectrum3_000497; Spectrum4_000616; Spectrum5_000958; Abitrexate (Methotrexate); METHOTREXATE [MI]; METHOTREXATE [INN]; METHOTREXATE [JAN]; METHOTREXATE [HSDB]; METHOTREXATE [USAN]; NCIMech_000767; SCHEMBL3711; Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)methylamino)benzoyl)-L-glutamova [Czech]; METHOTREXATE [VANDF]; BIDD:PXR0175; Lopac0_000020; KBioGR_001172; KBioSS_002341; Methotrexate Methylaminopterin; MLS000049968; MLS002154208; DivK1c_000114; METHOTREXATE [WHO-DD]; METHOTREXATE [WHO-IP]; SPBio_001094; SPBio_002149; Amethopterin (hydrate); CL14377 (hydrate); WR19039 (hydrate); AMY235; cid_126941; cid_165528; GTPL4674; GTPL4815; SCHEMBL12421860; SCHEMBL23111732; BDBM18050; BDBM66082; HMS500F16; KBio1_000114; KBio2_002338; KBio2_004906; KBio2_007474; KBio3_001493; Methotrexate (JP17/USP/INN); L01BA01; L04AX03; g301; NINDS_000114; Bio1_000486; Bio1_000975; Bio1_001464; HMS1568K12; HMS2095K12; HMS2233O18; HMS3260C21; HMS3414L09; HMS3678L07; HMS3712K12; METHOTREXATE [ORANGE BOOK]; APC-2002; BCP13701; GLUTAMIC ACID, N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)METHYLAMINO)BENZOYL)-, L-(+)-; MPI-5004; Tox21_110944; Tox21_300269; Tox21_500020; CCG-35800; EMT-25299; METHOTREXATUM [WHO-IP LATIN]; MFCD00064370; s1210; STL535338; (4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamic acid; AKOS016340329; Tox21_110944_1; CL14377; CS-1732; DB00563; KS-5093; LP00020; SDCCGSBI-0050009.P003; IDI1_000114; SMP2_000020; (methyl)amino)benzamido)pentanedioic acid; NCGC00025060-01; NCGC00025060-02; NCGC00025060-03; NCGC00025060-05; NCGC00025060-06; NCGC00025060-07; NCGC00025060-08; NCGC00025060-09; NCGC00025060-10; NCGC00025060-11; NCGC00025060-12; NCGC00025060-13; NCGC00025060-15; NCGC00025060-16; NCGC00254216-01; NCGC00260705-01; HY-14519; EU-0100020; FT-0601523; FT-0630651; G-301; NS00098764; SW198601-3; Methotrexate 1.0 mg/ml in Dimethyl Sulfoxide; C01937; D00142; EN300-119523; DL-4-Amino-N10-methylpteroylglutamic acid hydrate; Q422232; SR-01000597411; W-60383; (S)-2-(4-(((2,4-diaminopteridin-6-yl)methyl); Q-201366; SR-01000075682-1; SR-01000075682-2; SR-01000075682-6; SR-01000597411-1; W-105347; BRD-K59456551-001-09-3; BRD-K59456551-001-11-9; WLN: T66 BN DN GN JNJ CZ EZ H1N1&R DVMYVQ2VQ; Z1521553982; 4-AMINO-4-DEOXY-N(SUP 10)-METHYLPTEROYLGLUTAMATE; Methotrexate, European Pharmacopoeia (EP) Reference Standard; Methotrexate, United States Pharmacopeia (USP) Reference Standard; Glutamic acid,4-diamino-6-pteridinyl)methyl] methylamino]benzoyl]-, L-(+)-; L-Glutamic acid,4-diamino-6-pteridinyl)methyl]- methylamino]benzoyl]-; (S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)-(methyl)amino)benzamido)pentanedioic acid; GLUTAMIC ACID, N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)METHYLAMINO)BENZOYL)-,L; L-Glutamic acid,N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-,hydrate(9ci); Methotrexate for peak identification, European Pharmacopoeia (EP) Reference Standard; Methotrexate for system suitability, European Pharmacopoeia (EP) Reference Standard; Methotrexate, Pharmaceutical Secondary Standard; Certified Reference Material; N-(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)-L-glutamic acid; N-[4-[[(2,4-Diamino-6-pteridinyl)methyl] methylamino]benzoyl]-L-glutamic acid; (2S)-2-((4-(((2,4-DIAMINOPTERIDIN-6-YL)METHYL)(METHYL)AMINO)BENZOYL)AMINO)PENTANEDIOIC ACID; (2S)-2-[[[4-[(2,4-diamino-6-pteridinyl)methyl-methylamino]phenyl]-oxomethyl]amino]pentanedioic acid;hydrate; (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]glutaric acid;hydrate; (2S)-2-[[4-[[2,4-bis(azanyl)pteridin-6-yl]methyl-methyl-amino]phenyl]carbonylamino]pentanedioic acid;hydrate; 102613-64-9
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Target(s) Reduced folate transporter (SLC19A1)  Target Info 
Structure
Formula
C20H22N8O5
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 454.4
Lipid-water partition coefficient (xlogp) -1.8
Hydrogen Bond Donor Count (hbonddonor) 5
Hydrogen Bond Acceptor Count (hbondacc) 12
Rotatable Bond Count (rotbonds) 9
PubChem CID
126941
Canonical smiles
CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
InChI
InChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
InChIKey
FBOZXECLQNJBKD-ZDUSSCGKSA-N
IUPAC Name
(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid
The activity data of This Drug
Standard Type Value Administration times Cell line Cell line ID Ref.
Half Maximal Inhibitory Concentration (IC50) 3.29-0.44 µM 72 h HeLa cell CVCL_0030 [1]
Half Maximal Inhibitory Concentration (IC50) 10 µM 1 h Human coronary artery endothelial cell N.A. [2]
Half Maximal Inhibitory Concentration (IC50) 40 µM 72 h MDA-MB-231 cell CVCL_0062 [1]
Half Maximal Inhibitory Concentration (IC50) 500 µM 1 h Molt-3 T cell CVCL_0624 [2]
Half Maximal Effective Concentration (EC50) 8.2 nM N.A. CCRF-CEM cell CVCL_0207 [3]
Half Maximal Effective Concentration (EC50) 11.3 nM N.A. FaDu cell CVCL_1218 [4]
Half Maximal Effective Concentration (EC50) 12 nM N.A. CCRF-CEM cell CVCL_0207 [5]
Half Maximal Effective Concentration (EC50) 14 nM N.A. CCRF-CEM cell CVCL_0207 [6]
Half Maximal Effective Concentration (EC50) 14.4 nM N.A. CCRF-CEM cell CVCL_0207 [4]
Half Maximal Effective Concentration (EC50) 14.5 nM N.A. CCRF-CEM cell CVCL_0207 [7]
Half Maximal Effective Concentration (EC50) 15 nM N.A. CCRF-CEM cell CVCL_0207 [8]
Half Maximal Effective Concentration (EC50) 15.5 nM N.A. CCRF-CEM cell CVCL_0207 [9]
Half Maximal Effective Concentration (EC50) 17 nM N.A. FaDu cell CVCL_1218 [6]
Half Maximal Effective Concentration (EC50) 17.5 nM N.A. CCRF-CEM cell CVCL_0207 [10]
Half Maximal Effective Concentration (EC50) 18 nM N.A. CCRF-CEM cell CVCL_0207 [6]
Half Maximal Effective Concentration (EC50) 18 nM N.A. R30dm-CCRF-CEM cell CVCL_V325 [11]
Half Maximal Effective Concentration (EC50) 19 nM N.A. FaDu cell CVCL_1218 [11]
Half Maximal Effective Concentration (EC50) 31 nM N.A. FaDu cell CVCL_1218 [12]
Half Maximal Effective Concentration (EC50) 567 nM N.A. CCRF-CEM cell CVCL_0207 [13]
Half Maximal Effective Concentration (EC50) 595 nM N.A. CCRF-CEM cell CVCL_0207 [12]
Half Maximal Effective Concentration (EC50) 615 nM N.A. CCRF-CEM cell CVCL_0207 [7]
Half Maximal Effective Concentration (EC50) 620 nM N.A. CCRF-CEM cell CVCL_0207 [14]
Half Maximal Effective Concentration (EC50) 680 nM N.A. MV4-11 cell CVCL_0064 [10]
Half Maximal Effective Concentration (EC50) 720 nM N.A. R1 cell CVCL_2167 [11]
Half Maximal Effective Concentration (EC50) 900 nM N.A. MCF-7 cell CVCL_0031 [15]
Half Maximal Effective Concentration (EC50) 1.05 uM N.A. R1 cell CVCL_2167 [16]
Half Maximal Effective Concentration (EC50) 1.1 uM N.A. Caco-2 cell CVCL_0025 [15]
Half Maximal Effective Concentration (EC50) 1.5 uM N.A. CCRF-CEM cell CVCL_0207 [7]
Half Maximal Effective Concentration (EC50) 2.03 uM N.A. CCRF-CEM cell CVCL_0207 [9]
Half Maximal Effective Concentration (EC50) 2.63 uM N.A. R2-CCRF-CEM cell CVCL_S650 [17]
Half Maximal Effective Concentration (EC50) 2.76 uM N.A. CCRF-CEM cell CVCL_0207 [11]
Half Maximal Effective Concentration (EC50) 3.1 uM N.A. CCRF-CEM cell CVCL_0207 [12]
Half Maximal Effective Dosage (ED50) 2.4 nM N.A. HEp-2 cell CVCL_1906 [18]
Half Maximal Effective Dosage (ED50) 14.5 nM N.A. CCRF-CEM cell CVCL_0207 [19]
Half Maximal Effective Dosage (ED50) 15.5 nM N.A. CCRF-CEM cell CVCL_0207 [20]
Half Maximal Effective Dosage (ED50) 20 nM N.A. W256 cell CVCL_3537 [21]
Half Maximal Effective Dosage (ED50) <50 nM N.A. HL-60 cell CVCL_0002 [22]
Half Maximal Effective Dosage (ED50) 655 nM N.A. CCRF-CEM cell CVCL_0207 [20]
Half Maximal Growth Inhibition (GI50) 2.512 nM N.A. OVCAR-4 cell CVCL_1627 [23]
Half Maximal Growth Inhibition (GI50) 10 nM N.A. HCT 116 cell CVCL_0291 [24]
Half Maximal Growth Inhibition (GI50) 24 nM N.A. MCF-7 cell CVCL_0031 [25]
Half Maximal Growth Inhibition (GI50) 40 nM N.A. HT29 cell CVCL_A8EZ [26]
Half Maximal Growth Inhibition (GI50) 70 nM N.A. HT29 cell CVCL_A8EZ [24]
Half Maximal Growth Inhibition (GI50) 10.25 uM N.A. NCI-H226 cell CVCL_1544 [27]
Half Maximal Growth Inhibition (GI50) >100 uM N.A. HeLa cell CVCL_0030 [28]
Half Maximal Growth Inhibition (GI50) >100 uM N.A. HT29 cell CVCL_A8EZ [28]
Half Maximal Infective Dose (ID50) 3 ng/mL N.A. CCRF-CEM cell CVCL_0207 [29]
Half Maximal Infective Dose (ID50) 6 nmol/L N.A. CCRF-CEM cell CVCL_0207 [30]
Half Maximal Infective Dose (ID50) 8 mM N.A. TA3 cell CVCL_4315 [31]
Half Maximal Infective Dose (ID50) 3 nM N.A. CCRF-CEM cell CVCL_0207 [32]
Half Maximal Infective Dose (ID50) 10 nM N.A. L1210 cell CVCL_0382 [32]
Half Maximal Infective Dose (ID50) 20 nM N.A. Raji cell CVCL_0511 [33]
Half Maximal Infective Dose (ID50) 30 nM N.A. H9 cell CVCL_1240 [33]
Half Maximal Inhibitory Concentration (IC50) 0.23 ug/mL N.A. HT29 cell CVCL_A8EZ [34]
Half Maximal Inhibitory Concentration (IC50) 0.29 ug/mL N.A. NCI-H23 cell CVCL_1547 [35]
Half Maximal Inhibitory Concentration (IC50) 0.32 ug/mL N.A. Caco-2 cell CVCL_0025 [34]
Half Maximal Inhibitory Concentration (IC50) 2 ng/mL N.A. P388 cell CVCL_7222 [36]
Half Maximal Inhibitory Concentration (IC50) 4 ng/mL N.A. CCRF-CEM cell CVCL_0207 [37]
Half Maximal Inhibitory Concentration (IC50) 4.5 ug/mL N.A. Caki-1 cell CVCL_0234 [38]
Half Maximal Inhibitory Concentration (IC50) 10 ng/mL N.A. HT29 cell CVCL_A8EZ [36]
Half Maximal Inhibitory Concentration (IC50) 25 ug/mL N.A. Caki-1 cell CVCL_0234 [38]
Half Maximal Inhibitory Concentration (IC50) 27 ng/mL N.A. PC-3 cell CVCL_0035 [35]
Half Maximal Inhibitory Concentration (IC50) 35 ng/mL N.A. A-549 cell CVCL_0023 [39]
Half Maximal Inhibitory Concentration (IC50) 47.82 ug/mL N.A. HT29 cell CVCL_A8EZ [40]
Half Maximal Inhibitory Concentration (IC50) >60 ug/mL N.A. ZR-75-1 cell CVCL_0588 [35]
Half Maximal Inhibitory Concentration (IC50) 108 ug/mL N.A. M21 cell CVCL_D031 [38]
Half Maximal Inhibitory Concentration (IC50) 109 ug/mL N.A. M21 cell CVCL_D031 [38]
Half Maximal Inhibitory Concentration (IC50) 115 ug/mL N.A. M21 cell CVCL_D031 [38]
Half Maximal Inhibitory Concentration (IC50) 117 ug/mL N.A. M21 cell CVCL_D031 [38]
Half Maximal Inhibitory Concentration (IC50) 119 ug/mL N.A. M21 cell CVCL_D031 [38]
Half Maximal Inhibitory Concentration (IC50) 121 ug/mL N.A. M21 cell CVCL_D031 [38]
Half Maximal Inhibitory Concentration (IC50) 1 nM N.A. PC-3 cell CVCL_0035 [41]
Half Maximal Inhibitory Concentration (IC50) 2 nM N.A. PC-3 cell CVCL_0035 [42]
Half Maximal Inhibitory Concentration (IC50) 2.1 nM N.A. L1210 cell CVCL_0382 [43]
Half Maximal Inhibitory Concentration (IC50) 2.7 nM N.A. L1210 cell CVCL_0382 [44]
Half Maximal Inhibitory Concentration (IC50) 3.28 nM N.A. L1210 cell CVCL_0382 [45]
Half Maximal Inhibitory Concentration (IC50) 3.4 nM N.A. L1210 cell CVCL_0382 [46]
Half Maximal Inhibitory Concentration (IC50) 3.9 nM N.A. L1210 cell CVCL_0382 [47]
Half Maximal Inhibitory Concentration (IC50) 4.4 nM N.A. L1210 cell CVCL_0382 [48]
Half Maximal Inhibitory Concentration (IC50) 4.6 nM N.A. L1210 cell CVCL_0382 [49]
Half Maximal Inhibitory Concentration (IC50) 5 nM N.A. L1210 cell CVCL_0382 [50]
Half Maximal Inhibitory Concentration (IC50) 5 nM N.A. A-549 cell CVCL_0023 [41]
Half Maximal Inhibitory Concentration (IC50) 5.4 nM N.A. CCRF S-180 cell CVCL_2874 [51]
Half Maximal Inhibitory Concentration (IC50) 5.8 nM N.A. SCC-7 cell CVCL_V412 [52]
Half Maximal Inhibitory Concentration (IC50) 6 nM N.A. KB cell CVCL_0372 [53]
Half Maximal Inhibitory Concentration (IC50) 6.92 nM N.A. HL-60 cell CVCL_0002 [54]
Half Maximal Inhibitory Concentration (IC50) 7.5 nM N.A. SCC-25 cell CVCL_1682 [55]
Half Maximal Inhibitory Concentration (IC50) 8.1 nM N.A. HL-60 cell CVCL_0002 [56]
Half Maximal Inhibitory Concentration (IC50) 8.8 nM N.A. 143B cell CVCL_2270 [57]
Half Maximal Inhibitory Concentration (IC50) 8.9 nM N.A. HL-60 cell CVCL_0002 [58]
Half Maximal Inhibitory Concentration (IC50) 9 nM N.A. L1210 cell CVCL_0382 [56]
Half Maximal Inhibitory Concentration (IC50) 9.2 nM N.A. Vero cell CVCL_0059 [57]
Half Maximal Inhibitory Concentration (IC50) 9.5 nM N.A. NCI-H460 cell CVCL_0459 [57]
Half Maximal Inhibitory Concentration (IC50) 10 nM N.A. H35 cell CVCL_0285 [59]
Half Maximal Inhibitory Concentration (IC50) 10 nM N.A. L1210 cell CVCL_0382 [60]
Half Maximal Inhibitory Concentration (IC50) 10 nM N.A. KB cell CVCL_0372 [61]
Half Maximal Inhibitory Concentration (IC50) 12 nM N.A. L1210 cell CVCL_0382 [62]
Half Maximal Inhibitory Concentration (IC50) 12 nM N.A. U-373MG ATCC cell CVCL_2219 [57]
Half Maximal Inhibitory Concentration (IC50) 12 nM N.A. HL-60 cell CVCL_0002 [63]
Half Maximal Inhibitory Concentration (IC50) 12.6 nM N.A. Ehrlich cell CVCL_3873 [51]
Half Maximal Inhibitory Concentration (IC50) 13 nM N.A. A-549 cell CVCL_0023 [64]
Half Maximal Inhibitory Concentration (IC50) 13.1 nM N.A. SW620 cell CVCL_0547 [65]
Half Maximal Inhibitory Concentration (IC50) 13.5 nM N.A. A-549 cell CVCL_0023 [66]
Half Maximal Inhibitory Concentration (IC50) 15 nM N.A. SW480 cell CVCL_0546 [67]
Half Maximal Inhibitory Concentration (IC50) 18 nM N.A. HT29 cell CVCL_A8EZ [67]
Half Maximal Inhibitory Concentration (IC50) 19 nM N.A. KB cell CVCL_0372 [68]
Half Maximal Inhibitory Concentration (IC50) 20 nM N.A. KB cell CVCL_0372 [53]
Half Maximal Inhibitory Concentration (IC50) 21 nM N.A. IGROV-1 cell CVCL_1304 [69]
Half Maximal Inhibitory Concentration (IC50) 21 nM N.A. HeLa cell CVCL_0030 [58]
Half Maximal Inhibitory Concentration (IC50) 22 nM N.A. IGROV-1 cell CVCL_1304 [69]
Half Maximal Inhibitory Concentration (IC50) 22.7 nM N.A. HL-60 cell CVCL_0002 [66]
Half Maximal Inhibitory Concentration (IC50) 23 nM N.A. DU145 cell CVCL_0105 [42]
Half Maximal Inhibitory Concentration (IC50) 23 nM N.A. P388 cell CVCL_7222 [68]
Half Maximal Inhibitory Concentration (IC50) 23 nM N.A. A-549 cell CVCL_0023 [42]
Half Maximal Inhibitory Concentration (IC50) 24 nM N.A. L1210 cell CVCL_0382 [59]
Half Maximal Inhibitory Concentration (IC50) 25 nM N.A. WiDr cell CVCL_2760 [70]
Half Maximal Inhibitory Concentration (IC50) 25 nM N.A. HL-60 cell CVCL_0002 [71]
Half Maximal Inhibitory Concentration (IC50) 26 nM N.A. LOX IMVI cell CVCL_1381 [42]
Half Maximal Inhibitory Concentration (IC50) 27 nM N.A. SCC-25 cell CVCL_1682 [42]
Half Maximal Inhibitory Concentration (IC50) 28 nM N.A. MOLT-4 cell CVCL_0013 [72]
Half Maximal Inhibitory Concentration (IC50) 28 nM N.A. UACC-62 cell CVCL_1780 [72]
Half Maximal Inhibitory Concentration (IC50) 30 nM N.A. L1210 cell CVCL_0382 [73]
Half Maximal Inhibitory Concentration (IC50) 30 nM N.A. HCT 15 cell CVCL_0292 [72]
Half Maximal Inhibitory Concentration (IC50) 31 nM N.A. OVCAR-8 cell CVCL_1629 [42]
Half Maximal Inhibitory Concentration (IC50) 32 nM N.A. HT29 cell CVCL_A8EZ [42]
Half Maximal Inhibitory Concentration (IC50) 33 nM N.A. RPMI-8226 cell CVCL_7353 [72]
Half Maximal Inhibitory Concentration (IC50) 33 nM N.A. A-549 cell CVCL_0023 [72]
Half Maximal Inhibitory Concentration (IC50) 33 nM N.A. KM12 cell CVCL_1331 [72]
Half Maximal Inhibitory Concentration (IC50) 33 nM N.A. SW620 cell CVCL_0547 [42]
Half Maximal Inhibitory Concentration (IC50) 35 nM N.A. SF539 cell CVCL_1691 [72]
Half Maximal Inhibitory Concentration (IC50) 36 nM N.A. MCF-7 cell CVCL_0031 [72]
Half Maximal Inhibitory Concentration (IC50) 40 nM N.A. ACHN cell CVCL_1067 [72]
Half Maximal Inhibitory Concentration (IC50) 40 nM N.A. Raji cell CVCL_0511 [74]
Half Maximal Inhibitory Concentration (IC50) 40 nM N.A. RT-4 cell CVCL_0036 [75]
Half Maximal Inhibitory Concentration (IC50) 42 nM N.A. KM12 cell CVCL_1331 [42]
Half Maximal Inhibitory Concentration (IC50) 43 nM N.A. NCI-H23 cell CVCL_1547 [72]
Half Maximal Inhibitory Concentration (IC50) 45 nM N.A. DU145 cell CVCL_0105 [72]
Half Maximal Inhibitory Concentration (IC50) 50 nM N.A. MCF-7 cell CVCL_0031 [75]
Half Maximal Inhibitory Concentration (IC50) 52 nM N.A. SF268 cell CVCL_1689 [72]
Half Maximal Inhibitory Concentration (IC50) 63 nM N.A. U-251MG cell CVCL_0021 [72]
Half Maximal Inhibitory Concentration (IC50) 66 nM N.A. MC-38 cell CVCL_B288 [68]
Half Maximal Inhibitory Concentration (IC50) 66 nM N.A. P388 cell CVCL_7222 [76]
Half Maximal Inhibitory Concentration (IC50) 77 nM N.A. DAN-G cell CVCL_0243 [75]
Half Maximal Inhibitory Concentration (IC50) 78 nM N.A. NCI-ADR-RES cell CVCL_1452 [72]
Half Maximal Inhibitory Concentration (IC50) 87 nM N.A. SK-MEL-5 cell CVCL_0527 [72]
Half Maximal Inhibitory Concentration (IC50) 100 nM N.A. A-549 cell CVCL_0023 [77]
Half Maximal Inhibitory Concentration (IC50) 100 nM N.A. HeLa cell CVCL_0030 [78]
Half Maximal Inhibitory Concentration (IC50) 110 nM N.A. BGC-823 cell CVCL_3360 [78]
Half Maximal Inhibitory Concentration (IC50) 110 nM N.A. HCC 2998 cell CVCL_1266 [72]
Half Maximal Inhibitory Concentration (IC50) 120.5 nM N.A. R2 cell CVCL_C5SG [79]
Half Maximal Inhibitory Concentration (IC50) 121 nM N.A. R2 cell CVCL_C5SG [69]
Half Maximal Inhibitory Concentration (IC50) 150 nM N.A. SCC-25 cell CVCL_1682 [55]
Half Maximal Inhibitory Concentration (IC50) 191 nM N.A. UO-31 cell CVCL_1911 [42]
Half Maximal Inhibitory Concentration (IC50) 200 nM N.A. L1210 cell CVCL_0382 [80]
Half Maximal Inhibitory Concentration (IC50) 216 nM N.A. R2 cell CVCL_C5SG [69]
Half Maximal Inhibitory Concentration (IC50) 300 nM N.A. LNCaP cell CVCL_0395 [81]
Half Maximal Inhibitory Concentration (IC50) 398 nM N.A. OVCAR-3 cell CVCL_0465 [42]
Half Maximal Inhibitory Concentration (IC50) 400 nM N.A. OVCAR-3 cell CVCL_0465 [72]
Half Maximal Inhibitory Concentration (IC50) 450 nM N.A. NCI-H522 cell CVCL_1567 [72]
Half Maximal Inhibitory Concentration (IC50) 790 nM N.A. UACC-257 cell CVCL_1779 [72]
Half Maximal Inhibitory Concentration (IC50) 870 nM N.A. COLO205 cell CVCL_F402 [72]
Half Maximal Inhibitory Concentration (IC50) 980 nM N.A. OVCAR-5 cell CVCL_1628 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. RXF 393 cell CVCL_1673 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. OVCAR-4 cell CVCL_1627 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. R2 cell CVCL_C5SG [53]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. HOP-92 cell CVCL_1286 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. Malme-3M cell CVCL_1438 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. SK-MEL-2 cell CVCL_0069 [72]
Half Maximal Inhibitory Concentration (IC50) 1000 nM N.A. L1210 cell CVCL_0382 [62]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. T-47D cell CVCL_0553 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. Hs 578T cell CVCL_0332 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. SNB-75 cell CVCL_1706 [42]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. SK-MEL-28 cell CVCL_0526 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. BT-549 cell CVCL_1092 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. MDA-MB-435 cell CVCL_0417 [72]
Half Maximal Inhibitory Concentration (IC50) >1000 nM N.A. MV4-11 cell CVCL_0064 [72]
Half Maximal Inhibitory Concentration (IC50) 1.3 uM N.A. L1210 cell CVCL_0382 [82]
Half Maximal Inhibitory Concentration (IC50) 1.4 uM N.A. HT29 cell CVCL_A8EZ [81]
Half Maximal Inhibitory Concentration (IC50) 1.57 uM N.A. EL4 cell CVCL_0255 [83]
Half Maximal Inhibitory Concentration (IC50) 2.55 uM N.A. CCRF-CEM cell CVCL_0207 [52]
Half Maximal Inhibitory Concentration (IC50) 5.1 uM N.A. EL4 cell CVCL_0255 [84]
Half Maximal Inhibitory Concentration (IC50) 5.52 uM N.A. A-427 cell CVCL_1055 [75]
Half Maximal Inhibitory Concentration (IC50) 60 uM N.A. L1210 cell CVCL_0382 [85]
Half Maximal Inhibitory Concentration (IC50) 82.3 uM N.A. Bel-7402 cell CVCL_5492 [78]
Half Maximal Inhibitory Concentration (IC50) >100 uM N.A. HeLa cell CVCL_0030 [66]
Half Maximal Inhibitory Concentration (IC50) >100 uM N.A. MDA-MB-231 cell CVCL_0062 [86]
Half Maximal Inhibitory Concentration (IC50) 186 uM N.A. L1210 cell CVCL_0382 [48]
Half Maximal Inhibitory Concentration (IC50) 197 uM N.A. L1210 ( R81) cell CVCL_N028 [49]
Half Maximal Inhibitory Concentration (IC50) 220 uM N.A. L1210 cell CVCL_0382 [87]
Half Maximal Inhibitory Concentration (IC50) 419 uM N.A. K562 cell CVCL_0004 [88]
Half Maximal Lethal Concentration (IC50) 40 nM N.A. MCF-7 cell CVCL_0031 [89]
Each Peptide-drug Conjugate Related to This Drug
Full Information of The Activity Data of The PDC(s) Related to This Drug
STRAP-4-MTX [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Cervical cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.01 ± 0.22 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Endocervical adenocarcinoma HeLa cell CVCL_0030
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.34 ± 0.19 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Renal cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 50 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Normal HEK293 cell CVCL_0045
STRAP-3-MTX [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Cervical cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.22 ± 0.18 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

   Click to Show/Hide
Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Endocervical adenocarcinoma HeLa cell CVCL_0030
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.79 ± 0.31 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Renal cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 50 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Normal HEK293 cell CVCL_0045
STRAP-1-MTX [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Cervical cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.63 ± 0.28 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Endocervical adenocarcinoma HeLa cell CVCL_0030
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 2.26 ± 0.31 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Renal cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 50 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

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Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Normal HEK293 cell CVCL_0045
STRAP-2-MTX [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.82 ± 0.24 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

   Click to Show/Hide
Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Cervical cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 11.8 ± 2.28 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

   Click to Show/Hide
Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Endocervical adenocarcinoma HeLa cell CVCL_0030
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Renal cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 50 µM
Evaluation Method MTT assay
Administration Time 72 h
MOA of PDC
Electrostatics modulates the interactions of CPPs with the corresponding cell surface. Therefore, for the design of the amino acid side chain sequences, we reverse-engineered the spatial electrostatic potential distribution of the previously designed peptides with cell penetration ability. The spatial electrostatic fingerprints of the earlier designed peptides were generated as described previously. The reverse-engineered sequences with a shorter (7-mer) chain length were compared to the previous designs through multiple iterations of amino acid sequences. Their respective electrostatic profiles were used for the design of four syndiotactic, cationic, amphipathic peptides with optimal sequence selection. These syndiotactic re-engineered amphipathic peptides (STRAPs) were tested for their ability to penetrate cells and deliver a small molecule (methotrexate). The amino acid constitutions of STRAP-1, STRAP-2, STRAP-3, and STRAP-4 are the same. However, STRAP-2 is the stereochemically reversed STRAP-1; similarly, STRAP-4 is the stereochemically reversed STRAP-3. The use of LDLD and DLDL stereochemical sequences in the design of STRAPs resulted in the differential electrostatic signatures for the same amino acid sequences. The designed peptides have a higher cellular uptake in TNBC cells (MDA-MB-231) than the standard control TAT peptide. They could penetrate cells by both active and passive processes, and their activity is not reduced in biological fluids (human plasma and bovine serum). Furthermore, the delivery of MTX as STRAP-MTX conjugates helped to overcome the drug resistance of the MDA-MB-231 cells under in vitro conditions. The delivery of the STARP-4-MTX conjugate in TNBC xenograft tumors was more effective in the reduction of both the tumor size and metastasis to the lungs, liver, spleen, and lymph nodes.

   Click to Show/Hide
Description
To deliver the functional molecule into the cells, we attached an anticancer drug, methotrexate (MTX), to the N-terminus of STRAPs. The peptides were tested for their capability to deliver the active drug molecule in breast and cervical cancer cells. MDA-MB-231 and HeLa cells were treated with varying concentrations of MTX and STRAP-MTX conjugates for 72 h. Cell viability was assessed using the MTT assay. The cytotoxicity of MTX increased when delivered as peptide-MTX conjugates to the cells. This resulted in an overall reduction in the inhibitory concentration cytotoxic to 50% of cells (IC50) for MTX. The MTX resistance for MDA-MB-231 cells is well-established. The IC50 for MTX in MDA-MB-231 cells was minimum when delivered as a STRAP-4-MTX conjugate. Similar lowering of IC50 values in HeLa cells was observed. We also treated HEK-293 cells with MTX-STRAP conjugates. The peptide-drug conjugates showed no significant toxicity to the HEK-293 cells under the tested conditions, thereby confirming the earlier reported observation of higher uptake rates in cancerous cells.

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In Vitro Model Normal HEK293 cell CVCL_0045
PDC-5d [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 2.0 (5.7 ± 0.1) μM
In Vitro Model Breast adenocarcinoma MDA-MB-468 cell CVCL_0419
Experiment 2 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 4.2 (5.4 ± 0.1) μM
In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 3 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 5.0 (5.3 ± 0.1) μM
In Vitro Model Invasive breast carcinoma T-47D cell CVCL_0553
Experiment 4 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Effective Concentration (EC50) 8.9 nM
In Vitro Model Normal COS-7 cell CVCL_0224
PDC-5b [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 3.6 (5.4 ± 0.1) μM
In Vitro Model Breast adenocarcinoma MDA-MB-468 cell CVCL_0419
Experiment 2 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 7.7 (5.1 ± 0.1) μM
In Vitro Model Invasive breast carcinoma T-47D cell CVCL_0553
Experiment 3 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 8.1 (5.1 ± 0.1) μM
In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 4 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Effective Concentration (EC50) 3.0 (8.5 ± 0.1) nM
In Vitro Model Normal COS-7 cell CVCL_0224
Experiment 5 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Effective Concentration (EC50) 226 (6.6 ± 0.1) nM
In Vitro Model Normal COS-7 cell CVCL_0224
PDC-5c [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 3.8 (5.4 ± 0.1) μM
In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 2 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 4.0 (5.4 ± 0.1) μM
In Vitro Model Breast adenocarcinoma MDA-MB-468 cell CVCL_0419
Experiment 3 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10 µM
In Vitro Model Invasive breast carcinoma T-47D cell CVCL_0553
Experiment 4 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Effective Concentration (EC50) 2.8 (8.5 ± 0.1) nM
In Vitro Model Normal COS-7 cell CVCL_0224
PDC-5a [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 18 (4.8 ± 0.1) μM
In Vitro Model Breast adenocarcinoma MDA-MB-468 cell CVCL_0419
Experiment 2 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 25 µM
In Vitro Model Invasive breast carcinoma T-47D cell CVCL_0553
Experiment 3 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 25 µM
In Vitro Model Breast adenocarcinoma MDA-MB-231 cell CVCL_0062
Experiment 4 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Effective Concentration (EC50) 2.9 (8.5 ± 0.1) nM
In Vitro Model Normal COS-7 cell CVCL_0224
Experiment 5 Reporting the Activity Data of This PDC [90]
Indication Breast cancer
Efficacy Data Half Maximal Effective Concentration (EC50) 209 (6.7 ± 0.1) nM
In Vitro Model Normal COS-7 cell CVCL_0224
MTX-cLABL [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [2]
Indication Inflammation
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 µM
Evaluation Method Propidium iodide (PI) assay
Administration Time 1 h
MOA of PDC
In this study, cLABL and cLBEL peptides were linked to methotrexate (MTX) to produce MTX-cLABL and MTX-cLBEL conjugates. The goal was to target MTX to human coronary artery endothelial cells (HCAEC) via the ICAM-1 receptor to lower MTX toxicity and side effects. The biological abilities of MTX-cLABL, MTX-cLBEL, cLABL, cLBEL, and MTX were compared by their activities to inhibit binding of anti-ICAM-1 mAb to ICAM-1 on the surface of HCAEC. In addition, these molecules were compared in inhibiting T cell adhesion to HCAEC monolayers. Finally, their activities in suppressing IL-6 and IL-8 production as inflammatory cytokines were determined. The toxicities of MTX-cLABL and MTX-cLBEL conjugates were also determined relative to MTX alone as well as cLABL and cLBEL peptides.

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Description
We next determined whether treatment of HCAEC and Molt-3 T cells with peptides, MTX, and MTX-peptide conjugates resulted in inhibition of cell proliferation. Both HCAEC and Molt-3 T cells were affected by test compound in different levels. None of the molecules caused growth stimulation or total culture extinction. A net cell killing of HCAEC was observed upon treatment with MTX at all test concentrations while MTX affected net killing at ≥1.0 uM in Molt-3 T cells. The MTX-peptide conjugates were less toxic than MTX. In HCAEC, the net cell killing was at lower concentration for MTX at ≥0.1 uM compared to MTX-peptide conjugates at ≥500 uM. The net cell killing of Molt-3 T cells was found at ≥1.0 uM for MTX and ≥50 uM for MTX-peptide conjugates. For all test concentrations, the conjugates only resulted in HCAEC partial growth inhibition. For Molt-3 T cells, a total growth inhibition emerged at 100 uM for cLABL and cLBEL; however, 500 uM cLABL and cLBEL did not cause total cell killing for T cells.

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In Vitro Model human coronary artery endothelial cell Human coronary artery endothelial cell Homo sapiens
Experiment 2 Reporting the Activity Data of This PDC [2]
Indication Inflammation
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 500 µM
Evaluation Method Propidium iodide (PI) assay
Administration Time 1 h
MOA of PDC
In this study, cLABL and cLBEL peptides were linked to methotrexate (MTX) to produce MTX-cLABL and MTX-cLBEL conjugates. The goal was to target MTX to human coronary artery endothelial cells (HCAEC) via the ICAM-1 receptor to lower MTX toxicity and side effects. The biological abilities of MTX-cLABL, MTX-cLBEL, cLABL, cLBEL, and MTX were compared by their activities to inhibit binding of anti-ICAM-1 mAb to ICAM-1 on the surface of HCAEC. In addition, these molecules were compared in inhibiting T cell adhesion to HCAEC monolayers. Finally, their activities in suppressing IL-6 and IL-8 production as inflammatory cytokines were determined. The toxicities of MTX-cLABL and MTX-cLBEL conjugates were also determined relative to MTX alone as well as cLABL and cLBEL peptides.

   Click to Show/Hide
Description
We next determined whether treatment of HCAEC and Molt-3 T cells with peptides, MTX, and MTX-peptide conjugates resulted in inhibition of cell proliferation. Both HCAEC and Molt-3 T cells were affected by test compound in different levels. None of the molecules caused growth stimulation or total culture extinction. A net cell killing of HCAEC was observed upon treatment with MTX at all test concentrations while MTX affected net killing at ≥1.0 uM in Molt-3 T cells. The MTX-peptide conjugates were less toxic than MTX. In HCAEC, the net cell killing was at lower concentration for MTX at ≥0.1 uM compared to MTX-peptide conjugates at ≥500 uM. The net cell killing of Molt-3 T cells was found at ≥1.0 uM for MTX and ≥50 uM for MTX-peptide conjugates. For all test concentrations, the conjugates only resulted in HCAEC partial growth inhibition. For Molt-3 T cells, a total growth inhibition emerged at 100 uM for cLABL and cLBEL; however, 500 uM cLABL and cLBEL did not cause total cell killing for T cells.

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In Vitro Model Adult T acute lymphoblastic leukemia Molt-3 T cell CVCL_0624
MTX-cLBEL [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [2]
Indication Inflammation
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 µM
Evaluation Method Propidium iodide (PI) assay
Administration Time 1 h
MOA of PDC
In this study, cLABL and cLBEL peptides were linked to methotrexate (MTX) to produce MTX-cLABL and MTX-cLBEL conjugates. The goal was to target MTX to human coronary artery endothelial cells (HCAEC) via the ICAM-1 receptor to lower MTX toxicity and side effects. The biological abilities of MTX-cLABL, MTX-cLBEL, cLABL, cLBEL, and MTX were compared by their activities to inhibit binding of anti-ICAM-1 mAb to ICAM-1 on the surface of HCAEC. In addition, these molecules were compared in inhibiting T cell adhesion to HCAEC monolayers. Finally, their activities in suppressing IL-6 and IL-8 production as inflammatory cytokines were determined. The toxicities of MTX-cLABL and MTX-cLBEL conjugates were also determined relative to MTX alone as well as cLABL and cLBEL peptides.

   Click to Show/Hide
Description
We next determined whether treatment of HCAEC and Molt-3 T cells with peptides, MTX, and MTX-peptide conjugates resulted in inhibition of cell proliferation. Both HCAEC and Molt-3 T cells were affected by test compound in different levels. None of the molecules caused growth stimulation or total culture extinction. A net cell killing of HCAEC was observed upon treatment with MTX at all test concentrations while MTX affected net killing at ≥1.0 uM in Molt-3 T cells. The MTX-peptide conjugates were less toxic than MTX. In HCAEC, the net cell killing was at lower concentration for MTX at ≥0.1 uM compared to MTX-peptide conjugates at ≥500 uM. The net cell killing of Molt-3 T cells was found at ≥1.0 uM for MTX and ≥50 uM for MTX-peptide conjugates. For all test concentrations, the conjugates only resulted in HCAEC partial growth inhibition. For Molt-3 T cells, a total growth inhibition emerged at 100 uM for cLABL and cLBEL; however, 500 uM cLABL and cLBEL did not cause total cell killing for T cells.

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In Vitro Model human coronary artery endothelial cell Human coronary artery endothelial cell Homo sapiens
Experiment 2 Reporting the Activity Data of This PDC [2]
Indication Inflammation
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 500 µM
Evaluation Method Propidium iodide (PI) assay
Administration Time 1 h
MOA of PDC
In this study, cLABL and cLBEL peptides were linked to methotrexate (MTX) to produce MTX-cLABL and MTX-cLBEL conjugates. The goal was to target MTX to human coronary artery endothelial cells (HCAEC) via the ICAM-1 receptor to lower MTX toxicity and side effects. The biological abilities of MTX-cLABL, MTX-cLBEL, cLABL, cLBEL, and MTX were compared by their activities to inhibit binding of anti-ICAM-1 mAb to ICAM-1 on the surface of HCAEC. In addition, these molecules were compared in inhibiting T cell adhesion to HCAEC monolayers. Finally, their activities in suppressing IL-6 and IL-8 production as inflammatory cytokines were determined. The toxicities of MTX-cLABL and MTX-cLBEL conjugates were also determined relative to MTX alone as well as cLABL and cLBEL peptides.

   Click to Show/Hide
Description
We next determined whether treatment of HCAEC and Molt-3 T cells with peptides, MTX, and MTX-peptide conjugates resulted in inhibition of cell proliferation. Both HCAEC and Molt-3 T cells were affected by test compound in different levels. None of the molecules caused growth stimulation or total culture extinction. A net cell killing of HCAEC was observed upon treatment with MTX at all test concentrations while MTX affected net killing at ≥1.0 uM in Molt-3 T cells. The MTX-peptide conjugates were less toxic than MTX. In HCAEC, the net cell killing was at lower concentration for MTX at ≥0.1 uM compared to MTX-peptide conjugates at ≥500 uM. The net cell killing of Molt-3 T cells was found at ≥1.0 uM for MTX and ≥50 uM for MTX-peptide conjugates. For all test concentrations, the conjugates only resulted in HCAEC partial growth inhibition. For Molt-3 T cells, a total growth inhibition emerged at 100 uM for cLABL and cLBEL; however, 500 uM cLABL and cLBEL did not cause total cell killing for T cells.

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In Vitro Model Adult T acute lymphoblastic leukemia Molt-3 T cell CVCL_0624
References
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Ref 10 Benzoyl ring halogenated classical 2-amino-6-methyl-3,4-dihydro-4-oxo-5-substituted thiobenzoyl-7H-pyrrolo[2,3-d]pyrimidine antifolates as inhibitors of thymidylate synthase and as antitumor agents. J Med Chem. 2004 Dec 30;47(27):6730-9. doi: 10.1021/jm040144e.
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Ref 13 Synthesis and biological activities of tricyclic conformationally restricted tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases. J Med Chem. 1998 Apr 23;41(9):1409-16. doi: 10.1021/jm9705420.
Ref 14 Synthesis of classical, four-carbon bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates. J Med Chem. 2005 Aug 11;48(16):5329-36. doi: 10.1021/jm058213s.
Ref 15 Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231 cells. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5108-12. doi: 10.1016/j.bmcl.2010.07.024. Epub 2010 Jul 11.
Ref 16 Synthesis of N-[4-[1-ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid as an antifolate. J Med Chem. 2002 Apr 25;45(9):1942-8. doi: 10.1021/jm010575m.
Ref 17 Design, synthesis, and biological activities of classical N-[4-[2-(2-amino-4-ethylpyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid and its 6-methyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and as potential antitumor agents. J Med Chem. 2003 Feb 13;46(4):591-600. doi: 10.1021/jm0203534.
Ref 18 Convenient synthesis of 10-deazaaminopterin via a pteridine ylide. J Med Chem. 1980 Mar;23(3):320-1. doi: 10.1021/jm00177a022.
Ref 19 Synthesis and biological evaluation of N alpha-(4-amino-4-deoxy-10-methylpteroyl)-DL-4,4-difluoroornithine. J Med Chem. 1996 Jun 21;39(13):2536-40. doi: 10.1021/jm960046w.
Ref 20 Synthesis and biological evaluation of DL-4,4-difluoroglutamic acid and DL-gamma,gamma-difluoromethotrexate. J Med Chem. 1996 Jan 5;39(1):66-72. doi: 10.1021/jm950514m.
Ref 21 Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine. J Med Chem. 1980 Mar;23(3):327-9. doi: 10.1021/jm00177a025.
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