Drug Information

General Information of This Drug
Drug ID DRG00059
Drug Name Sunitinib
Synonyms
Sunitinib; 557795-19-4; Sutent; SU11248; SU-11248; sunitinibum; Su-011248; Sunitinib Base; 342641-94-5; (Z)-N-(2-(Diethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide; N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide; Sunitinib (INN); Sunitinib [INN]; NSC-750690; SU 11248; UNII-V99T50803M; CHEBI:38940; HSDB 7932; N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; CHEMBL535; N-(2-(Diethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide; NSC-736511; V99T50803M; SU011248; NSC750690; Sunitinib, Free base; NSC 736511; NSC 750690; 1H-Pyrrole-3-carboxamide, N-(2-(diethylamino)ethyl)-5-((Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-; n-(2-(diethylamino)ethyl)-5-((z)-(5-fluoro-1,2-dihydro-2-oxo-3h-indol-3-ylidene)methyl)-2,4-dimethyl-1h-pyrrole-3-carboxamide; N-(2-(DIETHYLAMINO)ETHYL)-5-((Z)-(5-FLUORO-2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-1H-PYRROLE-3-CARBOXAMIDE; Sunitinib (free base); Sunitinib [INN:BAN]; NCGC00164631-01; MFCD09260778; C22H27FN4O2; (Z)-Sunitinib; 1H-Pyrrole-3-carboxamide, N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-; 5-(5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylamino-ethyl)-amide; 5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylamino-ethyl)-amide; Sutent (free base); KS-5022; SUNITINIB [MI]; 1126641-10-8; SUNITINIB [VANDF]; SCHEMBL8081; SUNITINIB [WHO-DD]; SUNITINIB [EMA EPAR]; BDBM4814; GTPL5713; Sutent, Sunitinib, SU11248; DTXCID9021134; CHEBI:91430; EX-A553; L01XE04; WINHZLLDWRZWRT-ATVHPVEESA-N; BCPP000057; K00588a; (E)-N-[2-(Diethylamono)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indole-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; HY-10255A; NSC800937; s7781; AKOS015908193; AKOS025312424; CCG-268638; CS-1670; DB01268; NSC-800937; NCGC00164631-02; NCGC00164631-04; 5-(5-fluoro-2-oxo-1,2-dihydroindolylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide; BD164426; 1,2,4,5-tetramethylpyrrole-3-carboxamide; AM20090630; FT-0651493; FT-0659515; NS00004661; D08552; EN300-323230; AB01273976-01; AB01273976-02; AB01273976_04; A822143; A830806; Q417542; SR-00000000005; SR-00000000005-2; Q27163278; Z2568722545; 1H-Pyrrole-3-carboxamide,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-; 5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-diethylamino-ethyl)-amide; N-(2-(Diethylamino)ethyl)-5-((Z)-(5-fluoro-1 pound not2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2 pound not4-dimethyl-1H-pyrrole-3-carboxamide; N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carbo
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Target(s) Vascular endothelial growth factor receptor 2 (KDR)  Target Info 
Structure
Formula
C22H27FN4O2
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 398.5
Lipid-water partition coefficient (xlogp) 2.6
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 4
Rotatable Bond Count (rotbonds) 7
PubChem CID
5329102
Canonical smiles
CCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C
InChI
InChI=1S/C22H27FN4O2/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28)/b17-12-
InChIKey
WINHZLLDWRZWRT-ATVHPVEESA-N
IUPAC Name
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
The activity data of This Drug
Standard Type Value Disease Model Cell line Cell line ID Ref.
Half Maximal Effective Concentration (EC50) 900 nM Invasive breast carcinoma BT-474 cell CVCL_0179 [1]
Half Maximal Effective Concentration (EC50) 2.5 uM Pancreatic ductal adenocarcinoma BxPC-3 cell CVCL_0186 [1]
Half Maximal Growth Inhibition (GI50) 38 nM Gastrointestinal stromal tumor GIST-T1 cell CVCL_4976 [2]
Half Maximal Growth Inhibition (GI50) 2 uM Gastrointestinal stromal tumor GIST48 cell CVCL_7041 [3]
Half Maximal Growth Inhibition (GI50) 2 uM Gastrointestinal stromal tumor GIST430 cell CVCL_7040 [2]
Half Maximal Growth Inhibition (GI50) 4.789 uM Normal BaF3 cell CVCL_0161 [4]
Half Maximal Growth Inhibition (GI50) 5.88 uM Gastrointestinal stromal tumor GIST-T1 cell CVCL_4976 [5]
Half Maximal Inhibitory Concentration (IC50) 4.3 nM Acute monocytic leukemia MV4-11 cell CVCL_0064 [6]
Half Maximal Inhibitory Concentration (IC50) 9 nM Acute monocytic leukemia MV4-11 cell CVCL_0064 [7]
Half Maximal Inhibitory Concentration (IC50) 22.3 nM Breast adenocarcinoma MDA-MB-231 cell CVCL_0062 [8]
Half Maximal Inhibitory Concentration (IC50) 27.1 nM Invasive breast carcinoma MCF-7 cell CVCL_0031 [8]
Half Maximal Inhibitory Concentration (IC50) 29.3 nM Invasive breast carcinoma MCF-7 cell CVCL_0031 [8]
Half Maximal Inhibitory Concentration (IC50) 40 nM Thyroid gland medullary carcinoma TT cell CVCL_1774 [9]
Half Maximal Inhibitory Concentration (IC50) 500 nM Acute monocytic leukemia THP-1 cell CVCL_0006 [10]
Half Maximal Inhibitory Concentration (IC50) >1000 nM T acute lymphoblastic leukemia Jurkat cell CVCL_0065 [11]
Half Maximal Inhibitory Concentration (IC50) 1.01 uM Lung small cell carcinoma NCI-H526 cell CVCL_1569 [9]
Half Maximal Inhibitory Concentration (IC50) 2.5 uM Renal adenocarcinoma ACHN cell CVCL_1067 [12]
Half Maximal Inhibitory Concentration (IC50) 3.8 uM Colon cancer HT29 cell CVCL_A8EZ [13]
Half Maximal Inhibitory Concentration (IC50) 3.81 uM Hepatoblastoma Hep-G2 cell CVCL_0027 [10]
Half Maximal Inhibitory Concentration (IC50) >4 uM Lung large cell carcinoma NCI-H460 cell CVCL_0459 [10]
Half Maximal Inhibitory Concentration (IC50) 4.707 uM Hepatocellular carcinoma Huh-7 cell CVCL_0336 [14]
Half Maximal Inhibitory Concentration (IC50) 6.1 uM Colon carcinoma HCT 116 cell CVCL_0291 [15]
Half Maximal Inhibitory Concentration (IC50) 6.8 uM Invasive breast carcinoma MCF-7 cell CVCL_0031 [16]
Half Maximal Inhibitory Concentration (IC50) 6.98 uM Breast adenocarcinoma MDA-MB-231 cell CVCL_0062 [17]
Half Maximal Inhibitory Concentration (IC50) 7.981 uM Renal carcinoma A498 cell CVCL_1056 [14]
Half Maximal Inhibitory Concentration (IC50) 10.12 uM Lung carcinoid tumor NCI-H727 cell CVCL_1584 [14]
Half Maximal Inhibitory Concentration (IC50) 10.97 uM Lung adenocarcinoma PC-9 cell CVCL_B260 [18]
Half Maximal Inhibitory Concentration (IC50) 11.58 uM Amelanotic melanoma A-375 cell CVCL_0132 [18]
Half Maximal Inhibitory Concentration (IC50) 13.24 uM Hepatoblastoma Hep-G2 cell CVCL_0027 [18]
Half Maximal Inhibitory Concentration (IC50) 18.35 uM Colon carcinoma HCT 116 cell CVCL_0291 [18]
Half Maximal Inhibitory Concentration (IC50) 21.9 uM Chronic myeloid leukemia K562 cell CVCL_0004 [15]
Half Maximal Inhibitory Concentration (IC50) 25.1 uM Prostate carcinoma PC-3 cell CVCL_0035 [15]
Each Peptide-drug Conjugate Related to This Drug
Full Information of The Activity Data of The PDC(s) Related to This Drug
HR97-SunitiGel [Investigative]
 PDC Info 
Obtained from the Model Organism Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [19]
Indication Retinal injury
Efficacy Data RGC survival 692.2 ± 96.58 RGCs/mm2
Administration Time 4 week
MOA of PDC
In this work, we hypothesized that conjugation of the engineered multifunctional peptide adaptors to sunitinib for delivery to the posterior segment using the gel-forming eye drop would provide even more prolong therapeutic effects in the posterior tissues. We observed that the HR97-sunitinib conjugate had increased binding capacity to ocular melanin and was cleaved by proteases to release free sunitinib in vitro. Rats were dosed topically with HR97-SunitiGel once daily for seven days, followed by optic nerve head crush at various times after the last dose to assess the duration of RGC protection. We observed that the HR97-SunitiGel showed prolonged neuroprotective effects for up to 2 weeks after the last topical dose, whereas the protective effect of SunitiGel was only observed at 1 week after the last dose. Our observations support the potential for improving and prolonging therapeutic delivery to the posterior segment tissues by addressing multiple barriers to drug delivery and retention in the eye.

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Description
We next tested the potential duration of neuroprotection after topical dosing of HR97-SunitiGel. Brown Norway rats were dosed with HR97-SunitiGel or SunitiGel daily for 7 days, the optic nerve head crush procedure was performed on day 0, 7, or 21 after the last topical dose, and the RGC survival was characterized 7 days after the injury. The RGC quantification results computed by the cell counting program showed that the neuroprotective effect of HR97-SunitiGel lasted for at least 2 weeks after the last dose (869.2 ± 58.86 RGCs/mm2 compared to sham, 623.7 ± 70.39 RGCs/mm2), with the effect waning 4 weeks after the last dose (692.2 ± 96.58 RGCs/mm2). In contrast, SunitiGel provided significant RGC protection at 1 week (846.4 ± 125.8 RGCs/mm2) compared to the sham group, with protection waning 2 weeks after the last dose (717.3 ± 59.94 RGCs/mm2).

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In Vivo Model Brown norway rat optic nerve head (ONH) crush model.
Experiment 2 Reporting the Activity Data of This PDC [19]
Indication Retinal injury
Efficacy Data RGC survival 869.2 ± 58.86 RGCs/mm2
Administration Time 2 week
MOA of PDC
In this work, we hypothesized that conjugation of the engineered multifunctional peptide adaptors to sunitinib for delivery to the posterior segment using the gel-forming eye drop would provide even more prolong therapeutic effects in the posterior tissues. We observed that the HR97-sunitinib conjugate had increased binding capacity to ocular melanin and was cleaved by proteases to release free sunitinib in vitro. Rats were dosed topically with HR97-SunitiGel once daily for seven days, followed by optic nerve head crush at various times after the last dose to assess the duration of RGC protection. We observed that the HR97-SunitiGel showed prolonged neuroprotective effects for up to 2 weeks after the last topical dose, whereas the protective effect of SunitiGel was only observed at 1 week after the last dose. Our observations support the potential for improving and prolonging therapeutic delivery to the posterior segment tissues by addressing multiple barriers to drug delivery and retention in the eye.

   Click to Show/Hide
Description
We next tested the potential duration of neuroprotection after topical dosing of HR97-SunitiGel. Brown Norway rats were dosed with HR97-SunitiGel or SunitiGel daily for 7 days, the optic nerve head crush procedure was performed on day 0, 7, or 21 after the last topical dose, and the RGC survival was characterized 7 days after the injury. The RGC quantification results computed by the cell counting program showed that the neuroprotective effect of HR97-SunitiGel lasted for at least 2 weeks after the last dose (869.2 ± 58.86 RGCs/mm2 compared to sham, 623.7 ± 70.39 RGCs/mm2), with the effect waning 4 weeks after the last dose (692.2 ± 96.58 RGCs/mm2). In contrast, SunitiGel provided significant RGC protection at 1 week (846.4 ± 125.8 RGCs/mm2) compared to the sham group, with protection waning 2 weeks after the last dose (717.3 ± 59.94 RGCs/mm2).

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In Vivo Model Brown norway rat optic nerve head (ONH) crush model.
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