Drug Information

General Information of This Drug
Drug ID DRG00002
Drug Name Chlorambucil
Synonyms
chlorambucil; 305-03-3; Ambochlorin; Leukeran; Chloroambucil; Chloraminophen; Chlorbutin; Chloraminophene; Chlorobutine; Amboclorin; Ecloril; Chlorbutine; Chlorobutin; Lympholysin; Chlocambucil; Linfolizin; Linfolysin; Elcoril; Phenylbutyric acid nitrogen mustard; Leukersan; Leukoran; Chlorambucilum; NSC-3088; 4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid; Benzenebutanoic acid, 4-[bis(2-chloroethyl)amino]-; Cb l348; CB 1348; Phenylbuttersaeure-lost; 4-(4-(Bis(2-chloroethyl)amino)phenyl)butanoic acid; NSC 3088; Rcra waste number U035; NCI-C03485; 4-[p-[Bis(2-chloroethyl)amino]phenyl]butyric acid; N,N-Di-2-chloroethyl-gamma-p-aminophenylbutyric acid; CB-1348; 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid; 4-(Bis(2-chloroethyl)amino)benzenebutanoic acid; p-(N,N-Di-2-chloroethyl)aminophenyl butyric acid; 4-(p-Bis(beta-chloroethyl)aminophenyl)butyric acid; Benzenebutanoic acid, 4-(bis(2-chloroethyl)amino)-; CHEBI:28830; NSC3088; 4-[Bis(2-chloroethyl)aminophenyl]butyric acid; 4-[Bis(2-chloroethyl)amino]benzenebutyric acid; MFCD00021783; 4-[Bis(2-chloroethyl)amino]benzenebutanoic acid; CHEMBL515; 4-(p-(Bis(2-chloroethyl)amino)phenyl)butyric acid; gamma-[p-Di(2-chloroethyl)aminophenyl]butyric acid; MLS000028443; Chloorambucol; Chlorbutinum; DTXSID7020263; Elcorin; 4-(Bis(2-chloroethyl)amino)phenylbutyric acid; NCI-3088; gamma-(p-Di(2-chloroethyl)aminophenyl)butyric acid; Butyric acid, 4-(p-bis(2-chloroethyl)aminophenyl)-; 18D0SL7309; Kyselina 4-(N,N-bis-(2-chlorethyl)-p-aminofenyl)maselna; NCGC00015199-08; Clorambucile; Clorambucilo; CAS-305-03-3; SMR000058372; Clorambucile [DCIT]; Leukeran tablets; 4-[Bis(2-chloroethyl)amino]phenylbutyric acid; DTXCID30263; 4-(4-[Bis(2-chloroethyl)amino]phenyl)butyric acid; .gamma.-[p-Di(2-chloroethyl)aminophenyl]butyric acid; Butyric acid, 4-[p-[bis(2-chloroethyl)amino]phenyl]-; Chlorambucilum [INN-Latin]; Clorambucilo [INN-Spanish]; p-N,N-Di-(.beta.-chloroethyl)aminophenyl butyric acid; N,N-Di-2-chloroethyl-.gamma.-p-aminophenylbutyric acid; C14H19Cl2NO2; CCRIS 126; Phenylbuttersaeure-lost [German]; HSDB 3026; SR-01000000062; LEUKERAN (TN); 4-[4-[Bis(2-chloroethyl)amino]phenyl]butyric Acid; EINECS 206-162-0; .gamma.-(p-bis(2-chloroethyl)aminophenyl)butyric acid; .gamma.-[p-bis(2-chloroethyl)aminophenyl]butyric acid; 4-(p-Bis(.beta.-chloroethyl)aminophenyl)butyric acid; 4-[p-Bis(.beta.-chloroethyl)aminophenyl]butyric acid; RCRA waste no. U035; Butyric acid, 4-(p-[bis(2-chloroethyl)amino]phenyl)-; BRN 0999011; chlorambucilddv; gamma-(p-Bis(2-chloroethyl)aminophenyl)butyric acid; Chlorambucil [USP:INN:BAN]; AI3-26083; UNII-18D0SL7309; p-(N,N-Di-2-chlorethylaminophenyl)butyric acid; para-(Di(2-chloroethyl)aminophenyl)butyric acid; Chlorambucil,(S); gamma-(p-bis(2-chloroethyl)aminophenyl)butyricacid; Butanoic acid, 4-(bis(2-chloroethyl)amino) benzene; phenyl)butanoic acid; p-N,N-Di-(beta-chloroethyl)aminophenyl butyric acid; Butyric acid, 4-(p-(bis(2-chloroethyl)amino)phenyl); para-N,N-Di(beta-chloroethyl)aminophenyl butyric acid; N,N-Di-2-chloroethyl-gamma-para-aminophenyl butyric acid; Opera_ID_51; Spectrum_000118; Kyselina 4-(N,N-bis-(2-chlorethyl)-p-aminofenyl)maselna [Czech]; Prestwick0_001079; Prestwick1_001079; Prestwick2_001079; Prestwick3_001079; Spectrum2_000065; Spectrum3_000336; Spectrum4_000273; Spectrum5_000677; CHLORAMBUCIL [MI]; Lopac-C-0253; CHLORAMBUCIL [INN]; CHLORAMBUCIL [JAN]; Epitope ID:139977; CHLORAMBUCIL [HSDB]; CHLORAMBUCIL [IARC]; SCHEMBL4308; CHLORAMBUCIL [VANDF]; Chlorambucil with impurity G; Lopac0_000227; WLN: QV3R DN2G2G; BSPBio_001098; BSPBio_001971; CHLORAMBUCIL [MART.]; KBioGR_000766; KBioSS_000558; 4-14-00-01715 (Beilstein Handbook Reference); MLS001076130; CHLORAMBUCIL [USP-RS]; CHLORAMBUCIL [WHO-DD]; CHLORAMBUCIL [WHO-IP]; DivK1c_000688; SPECTRUM1500171; Chlorambucil (JAN/USP/INN); SPBio_000249; SPBio_002999; BPBio1_001208; GTPL7143; HMS502C10; KBio1_000688; KBio2_000558; KBio2_003126; KBio2_005694; KBio3_001191; NINDS_000688; CHLORAMBUCIL [ORANGE BOOK]; Chlorambucil for system suitability; HMS1571G20; HMS1920M15; HMS2090M19; HMS2091A22; HMS2098G20; HMS2235A04; HMS3259I10; HMS3372O04; HMS3652P08; Pharmakon1600-01500171; 4-(4-(bis(2-chloroethyl)amino); CHLORAMBUCIL [EP MONOGRAPH]; AMY33445; BCP28394; CHLORAMBUCIL [USP MONOGRAPH]; Tox21_110096; Tox21_201390; Tox21_302996; BDBM50003677; CCG-39872; NSC756674; s4288; CHLORAMBUCILUM [WHO-IP LATIN]; AKOS024319346; Tox21_110096_1; Chlorambucil, purum, >=98.0% (T); CS-3118; DB00291; GS-6200; LP00227; NC00555; NSC-756674; SDCCGSBI-0050215.P005; IDI1_000688; NCGC00015199-01; NCGC00015199-02; NCGC00015199-03; NCGC00015199-04; NCGC00015199-05; NCGC00015199-06; NCGC00015199-07; NCGC00015199-09; NCGC00015199-10; NCGC00015199-11; NCGC00015199-12; NCGC00015199-13; NCGC00015199-14; NCGC00015199-15; NCGC00015199-16; NCGC00015199-17; NCGC00015199-19; NCGC00015199-20; NCGC00023250-00; NCGC00023250-03; NCGC00023250-04; NCGC00023250-05; NCGC00023250-06; NCGC00023250-07; NCGC00023250-08; NCGC00023250-09; NCGC00023250-10; NCGC00256464-01; NCGC00258941-01; BP-24028; HY-13593; NCI60_002639; SY031075; SBI-0050215.P004; DB-047794; AB00051938; C2939; EU-0100227; FT-0617365; NS00009960; SW197258-4; A18607; C 0253; C06900; D00266; EN300-123640; H10484; AB00051938-14; AB00051938-15; AB00051938_16; Q415939; 4-(4-(Bis(2-chloroethyl)amino)phenyl)butanoicacid; 4[p-Bis(.beta.-chloroethyl)aminophenyl]butyric acid; Butanoic acid, 4-(bis(2-chloroethyl)amino)benzene-; SR-01000000062-2; SR-01000000062-4; SR-01000000062-7; W-106940; .gamma.-(p-bis(2-chloroethyl)aminophenyl)butyricacid; BRD-K29458283-001-04-2; BRD-K29458283-001-05-9; BRD-K29458283-001-17-4; 4-(4-[Bis(2-chloroethyl)amino]phenyl)butanoic acid #; Z1552153009; 4-[4-(N,N-bis(2-chloroethyl)-amino]phenyl)butanoic acid; Chlorambucil, European Pharmacopoeia (EP) Reference Standard; Chlorambucil, United States Pharmacopeia (USP) Reference Standard; Chlorambucil for system suitability, European Pharmacopoeia (EP) Reference Standard
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Target(s) DNA topoisomerase 2-alpha (TOP2A)  Target Info 
Structure
Formula
C14H19Cl2NO2
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 304.2
Lipid-water partition coefficient (xlogp) 1.7
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
Rotatable Bond Count (rotbonds) 9
PubChem CID
2708
Canonical smiles
C1=CC(=CC=C1CCCC(=O)O)N(CCCl)CCCl
InChI
InChI=1S/C14H19Cl2NO2/c15-8-10-17(11-9-16)13-6-4-12(5-7-13)2-1-3-14(18)19/h4-7H,1-3,8-11H2,(H,18,19)
InChIKey
JCKYGMPEJWAADB-UHFFFAOYSA-N
IUPAC Name
4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid
The activity data of This Drug
Standard Type Value Administration times Cell line Cell line ID Ref.
Half Maximal Inhibitory Concentration (IC50) 154.4 µM 48 h Hep-G2 cell CVCL_0027 [1]
Half Maximal Inhibitory Concentration (IC50) 192.5 µM 48 h Bel-7402 cell CVCL_5492 [1]
Half Maximal Inhibitory Concentration (IC50) 214.6 µM 48 h MCF-7 cell CVCL_0031 [1]
Each Peptide-drug Conjugate Related to This Drug
Full Information of The Activity Data of The PDC(s) Related to This Drug
CRB-FFE-YSV [Investigative]
 PDC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [2]
Indication Tumor
Efficacy Data Relative tumor volume of mice 356%
Administration Time Day 1, day 4, day 7, and day 10
Administration Dosage 10 µmol/kg
Description
After treatment for 28 days, the final relative tumor volume of mice treated with PBS, YSV, CRB, YSV + CRB, or CRB-FFE-YSV hydrogel was 927, 728, 491, 514, and 356%, respectively.
In Vivo Model HepG2-tumor-bearing BALB/c nude mice.
In Vitro Model Hepatoblastoma L-O2 cell line CVCL_0027
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 [2]
Indication Tumor
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 25.7 µM
Evaluation Method MTT assay
Administration Time 48 h
Description
The corresponding IC50 values of CRB-FFE-YSV nanofibers against HepG2, MCF-7, and BEL-7402 cells were 28.9, 47.5, and 25.7 um, respectively, which were much lower than that of free YSV (842.9, 999.5, and 719.2 um), free CRB (154.4, 214.6, and 192.5 um), and the mixed drugs (150.0, 190.3, and 180.6 um).
In Vitro Model Hepatoma Bel-7402 cell CVCL_5492
Experiment 2 Reporting the Activity Data of This PDC [2]
Indication Tumor
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 28.9 µM
Evaluation Method MTT assay
Administration Time 48 h
Description
The corresponding IC50 values of CRB-FFE-YSV nanofibers against HepG2, MCF-7, and BEL-7402 cells were 28.9, 47.5, and 25.7 um, respectively, which were much lower than that of free YSV (842.9, 999.5, and 719.2 um), free CRB (154.4, 214.6, and 192.5 um), and the mixed drugs (150.0, 190.3, and 180.6 um).
In Vitro Model Hepatoblastoma Hep-G2 cell CVCL_0027
Experiment 3 Reporting the Activity Data of This PDC [2]
Indication Tumor
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 47.5 µM
Evaluation Method MTT assay
Administration Time 48 h
Description
The corresponding IC50 values of CRB-FFE-YSV nanofibers against HepG2, MCF-7, and BEL-7402 cells were 28.9, 47.5, and 25.7 um, respectively, which were much lower than that of free YSV (842.9, 999.5, and 719.2 um), free CRB (154.4, 214.6, and 192.5 um), and the mixed drugs (150.0, 190.3, and 180.6 um).
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
CRB-FFFK-cyclen [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 24 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Half maximal inhibitory concentration (IC50) 23.8 μM
Evaluation Method MTT assay
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

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Description
The IC50 values of CRB-FFFK-cyclen nanofiber against A549 cells, HeLa cells and MCF-7 cells were 23.8, 50.2, and 127.4 μM, respectively.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 2 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Half maximal inhibitory concentration (IC50) 50.2 μM
Evaluation Method MTT assay
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

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Description
The IC50 values of CRB-FFFK-cyclen nanofiber against A549 cells, HeLa cells and MCF-7 cells were 23.8, 50.2, and 127.4 μM, respectively.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 3 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Half maximal inhibitory concentration (IC50) 127.4 μM
Evaluation Method MTT assay
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
The IC50 values of CRB-FFFK-cyclen nanofiber against A549 cells, HeLa cells and MCF-7 cells were 23.8, 50.2, and 127.4 μM, respectively.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 4 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 15.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 500 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 5 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 15.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 500 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 6 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 20.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 250 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 7 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 20.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 250 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 8 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 20.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 500 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 9 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 28.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 125 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 10 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 30.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 62.5 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

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Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 11 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 30.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 125 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 12 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 35.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 31.3 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 13 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 40.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 250 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 14 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 50.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 125 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 15 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 55.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 62.5 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 16 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 60.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 15.6 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 17 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 60.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 31.3 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 18 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 62.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 15.6 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 19 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 64.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 7.8 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Human papillomavirus-related cervical adenocarcinoma HeLa cell CVCL_0030
Experiment 20 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 70.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 62.5 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 21 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 78.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 7.8 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Lung adenocarcinoma A-549 cell CVCL_0023
Experiment 22 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 78.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 31.3 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 23 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 80.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 15.6 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
Experiment 24 Reporting the Activity Data of This PDC [3]
Indication Solid tumor
Efficacy Data Cell viability 83.00%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 7.8 μM
MOA of PDC
The DNA-alkylating agent chlorambucil (CRB) belongs to aryl nitrogen mustard antitumor drugs, and has been widely used for treating different types of cancerous diseases. However, the clinical application of CRB is severely restricted by its poor aqueous solubility, lack of targeting, short degradation half-life and severe side effects. Macrocyclic polyamines have many applications in medicine, industry and other fields, owing to their chemical and biological properties. Some of them, such as cyclen and cyclam, could be protonated below physiological pH (7.4), and the lower the pH, the higher the degree of protonation. It is reported that the pH of the tumor environment is lower than the physiological pH, which is beneficial to the protonation of macrocyclic polyamines. Modification of macrocyclic polyamine to self-assembling peptide-drug amphiphiles can increase the cell accumulation of the hydrogel, because the cationic hydrogel has a high affinity to a negatively charged cell membrane and nucleus. Therefore, a macrocyclic polyamine containing peptide hydrogel could serve as a suitable delivery system to improve the pharmacokinetic properties of CRB, achieving improved delivery efficacy and enhanced antitumor activity without severe side effects. Herein, we report a self-assembling peptide-based cationic supramolecular nanomedicine bearing the small molecule agent CRB and macrocyclic polyamine cyclen. We found that the CRB-FFFK-cyclen conjugate could readily transform into a hydrogel through a heating-cooling process, and the resulting hydrogel could significantly improve drug stability, cellular uptake and, antitumor activity.

   Click to Show/Hide
Description
CRB and CRB-FFFK-cyclen hydrogel both exhibited broad-spectrum anticancer activities against different types of cancer cells in a dose-dependent manner.
In Vitro Model Invasive breast carcinoma MCF-7 cell CVCL_0031
99mTc-HYNIC-CLB-c(NGR) [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 [4]
Indication Melanoma
Efficacy Data Growth inhibition rate 30%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 1 µM
Description
The exposure of cells to PDC resulted in significant growth inhibition at all the concentrations as compared to the drug or the peptide alone. It was observed that nearly 25-fold excess concentration of the drug is required to achieve similar cytotoxicity as obtained on exposure to PDC. The RGD peptide-CLB conjugate has also been reported to show higher growth inhibition in B16F10 cells as compared to the drug or peptide alone.24 The enhanced cytotoxic effect of PDC even at lower levels indicates clear advantage in reducing the systemic exposure and side effects of the drug.

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In Vitro Model Mouse melanoma B16-F10 cell CVCL_0159
Experiment 2 Reporting the Activity Data of This PDC [4]
Indication Melanoma
Efficacy Data Growth inhibition rate 33%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 5 µM
MOA of PDC
Although RNT with 177Lu-DOTATATE/PSMA is known as a novel and effective therapy option for cancer that significantly improves the quality of life and survival of patients, it may have acute or chronic side effects. Therefore, any method that can ameliorate these side effects is useful in the RNT process. For this purpose, a few clinical studies have reported that antioxidants as free radical scavengers such as amifostine and vitamins C and E can reduce radioiodine-related side effects, particularly in salivary glands in thyroid cancer patients.

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Description
The exposure of cells to PDC resulted in significant growth inhibition at all the concentrations as compared to the drug or the peptide alone. It was observed that nearly 25-fold excess concentration of the drug is required to achieve similar cytotoxicity as obtained on exposure to PDC. The RGD peptide-CLB conjugate has also been reported to show higher growth inhibition in B16F10 cells as compared to the drug or peptide alone.24 The enhanced cytotoxic effect of PDC even at lower levels indicates clear advantage in reducing the systemic exposure and side effects of the drug.

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In Vitro Model Mouse melanoma B16-F10 cell CVCL_0159
Experiment 3 Reporting the Activity Data of This PDC [4]
Indication Melanoma
Efficacy Data Growth inhibition rate 40%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 10 µM
Description
The exposure of cells to PDC resulted in significant growth inhibition at all the concentrations as compared to the drug or the peptide alone. It was observed that nearly 25-fold excess concentration of the drug is required to achieve similar cytotoxicity as obtained on exposure to PDC. The RGD peptide-CLB conjugate has also been reported to show higher growth inhibition in B16F10 cells as compared to the drug or peptide alone.24 The enhanced cytotoxic effect of PDC even at lower levels indicates clear advantage in reducing the systemic exposure and side effects of the drug.

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In Vitro Model Mouse melanoma B16-F10 cell CVCL_0159
Experiment 4 Reporting the Activity Data of This PDC [4]
Indication Melanoma
Efficacy Data Growth inhibition rate 55%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 25 µM
Description
The exposure of cells to PDC resulted in significant growth inhibition at all the concentrations as compared to the drug or the peptide alone. It was observed that nearly 25-fold excess concentration of the drug is required to achieve similar cytotoxicity as obtained on exposure to PDC. The RGD peptide-CLB conjugate has also been reported to show higher growth inhibition in B16F10 cells as compared to the drug or peptide alone.24 The enhanced cytotoxic effect of PDC even at lower levels indicates clear advantage in reducing the systemic exposure and side effects of the drug.

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In Vitro Model Mouse melanoma B16-F10 cell CVCL_0159
Experiment 5 Reporting the Activity Data of This PDC [4]
Indication Melanoma
Efficacy Data Growth inhibition rate 75%
Evaluation Method MTT assay
Administration Time 48 h
Administration Dosage 50 µM
Description
The exposure of cells to PDC resulted in significant growth inhibition at all the concentrations as compared to the drug or the peptide alone. It was observed that nearly 25-fold excess concentration of the drug is required to achieve similar cytotoxicity as obtained on exposure to PDC. The RGD peptide-CLB conjugate has also been reported to show higher growth inhibition in B16F10 cells as compared to the drug or peptide alone.24 The enhanced cytotoxic effect of PDC even at lower levels indicates clear advantage in reducing the systemic exposure and side effects of the drug.

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In Vitro Model Mouse melanoma B16-F10 cell CVCL_0159
P6-chlorambucil [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [5]
Indication Tumor
Efficacy Data A20 growth inhibition 22.00%
Evaluation Method XTT assay
Administration Time 72 h
Administration Dosage 50 µM
Description
Conjugation of the drugs to P4 affected their efficacy toward A20 cells. For chlorambucil and melphalan, conjugation reduced the cytotoxic effect and this was significant for chlorambucil at 25 μM (p = 0.0013). On the other hand, conjugation significantly improved the cytotoxic effect of bendamustine at 25 (p = 0.043) and 50 μM (p = 0.048). The efficacies of all P6-conjugates were significantly lower than those of P4-conjugates at concentrations above 10 μM.

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In Vitro Model Mouse reticulum cell sarcoma A20 cell CVCL_1940
P4-Chlor-PEG-AuNP [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 [5]
Indication Tumor
Efficacy Data A20 growth inhibition 40.00%
Evaluation Method XTT assay
Administration Time 72 h
Administration Dosage 50 µM
Description
All three P4-PDC-coated gold nanoparticles pre-incubated for 24 or 48 h induced statistically similar cytotoxicity in A20 to that induced by freshly prepared PDC4 and to coated particles without pre-incubation (the latter data not shown).
In Vitro Model Mouse reticulum cell sarcoma A20 cell CVCL_1940
Experiment 2 Reporting the Activity Data of This PDC [5]
Indication Tumor
Efficacy Data A20 growth inhibition 72.00%
Evaluation Method XTT assay
Administration Time 48 h
Administration Dosage 50 µM
MOA of PDC
In biological systems, antioxidants such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase are responsible for the elimination or reduction of the adverse effects of ROS, that is, they prevent or reduce ROS generation. Dietary antioxidants, such as vitamins E, A, and C, and anthocyanins and polyphenols have a role in the protection of cells against ROS damage.

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Description
All three P4-PDC-coated gold nanoparticles pre-incubated for 24 or 48 h induced statistically similar cytotoxicity in A20 to that induced by freshly prepared PDC4 and to coated particles without pre-incubation (the latter data not shown).
In Vitro Model Mouse reticulum cell sarcoma A20 cell CVCL_1940
Experiment 3 Reporting the Activity Data of This PDC [5]
Indication Tumor
Efficacy Data A20 growth inhibition 80.00%
Evaluation Method XTT assay
Administration Time 24 h
Administration Dosage 50 µM
Description
All three P4-PDC-coated gold nanoparticles pre-incubated for 24 or 48 h induced statistically similar cytotoxicity in A20 to that induced by freshly prepared PDC4 and to coated particles without pre-incubation (the latter data not shown).
In Vitro Model Mouse reticulum cell sarcoma A20 cell CVCL_1940
P4-chlorambucil [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [5]
Indication Tumor
Efficacy Data A20 growth inhibition 70.00%
Evaluation Method XTT assay
Administration Time 72 h
Administration Dosage 50 µM
Description
Conjugation of the drugs to P4 affected their efficacy toward A20 cells. For chlorambucil and melphalan, conjugation reduced the cytotoxic effect and this was significant for chlorambucil at 25 μM (p = 0.0013). On the other hand, conjugation significantly improved the cytotoxic effect of bendamustine at 25 (p = 0.043) and 50 μM (p = 0.048). The efficacies of all P6-conjugates were significantly lower than those of P4-conjugates at concentrations above 10 μM.

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In Vitro Model Mouse reticulum cell sarcoma A20 cell CVCL_1940
References
Ref 1 Correction to "Supramolecular Hydrogel Based on Chlorambucil and Peptide Drug for Cancer Combination Therapy". ACS Appl Mater Interfaces. 2024 Feb 28;16(8):11145. doi: 10.1021/acsami.4c00456. Epub 2024 Feb 15. Erratum for: ACS Appl Mater Interfaces. 2019 Jan 9;11(1):331-339. doi: 10.1021/acsami.8b18425.
Ref 2 Supramolecular Hydrogel Based on Chlorambucil and Peptide Drug for Cancer Combination Therapy. ACS Appl Mater Interfaces. 2019 Jan 9;11(1):331-339. doi: 10.1021/acsami.8b18425. Epub 2018 Dec 28.
Ref 3 A peptide-drug hydrogel to enhance the anti-cancer activity of chlorambucil. Biomater Sci. 2020 Oct 21;8(20):5638-5646. doi: 10.1039/d0bm01001d. Epub 2020 Sep 18.
Ref 4 (99m) Tc-labeled NGR-chlorambucil conjugate, (99m) Tc-HYNIC-CLB-c(NGR) for targeted chemotherapy and molecular imaging. J Labelled Comp Radiopharm. 2017 Jul;60(9):431-438. doi: 10.1002/jlcr.3522. Epub 2017 Jun 21.
Ref 5 Gold nanoparticles stabilize peptide-drug-conjugates for sustained targeted drug delivery to cancer cells. J Nanobiotechnology. 2018 Mar 30;16(1):34. doi: 10.1186/s12951-018-0362-1.