Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C24H29FN4O2 |
| Molecular Weight | 424.5111 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN(CC)CCNC(=O)C1=C(C)NC2=C1CCC\C2=C3\C(=O)NC4=C3C=C(F)C=C4
InChI
InChIKey=KGSRYTUWXUESJK-FXBPSFAMSA-N
InChI=1S/C24H29FN4O2/c1-4-29(5-2)12-11-26-23(30)20-14(3)27-22-16(20)7-6-8-17(22)21-18-13-15(25)9-10-19(18)28-24(21)31/h9-10,13,27H,4-8,11-12H2,1-3H3,(H,26,30)(H,28,31)/b21-17-
| Molecular Formula | C24H29FN4O2 |
| Molecular Weight | 424.5111 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
SIM-010603 (Tafetinib) is a structurally novel, oral, multi-targeted receptor tyrosine kinase inhibitor. SIM-010603 inhibited stem cell factor receptor (Kit), vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β), glial cell line-derived neurotrophic factor receptor (Rearranged during Transfection; RET), and Fms-like tyrosine kinase-3 (FLT3) with IC(50) values between 5.0 and 68.1 nmol/l. SIM010603 inhibited the phosphorylation of PDGFR-β and VEGFR-2. Moreover, SIM-010603 inhibited endothelial cell proliferation, endothelial cells chemotaxis, and corneal angiogenesis. SIM-010603 inhibited tumor growth in these xenograft tumor growth models. SIM010603 reduced tumor MVD in T241-VEGF-A tumor xenograft models and decreased positive signals of CD31, NG2 in MDA-MB-435, and LLC-SW-44 xenograft tumor models. SIM-010603 was in development by Simcere Pharmaceutical Group for the cancer treatment. It was in phase I clinical trials by Simcere, Jilin Boda Pharma and Nanjing Yoko Biological Pharma for the treatment of solid tumours, but this research was discontinued.
Originator
Approval Year
Sample Use Guides
The subchronic toxicity of SIM-010603 in SD rats and beagle dogs have been characterized. Rats and dogs received SIM-010603 orally (0-20 and 0-10mg/kg/day, respectively) on a consecutive daily dosing schedule for 28 days following a 14 days recovery period.
Route of Administration:
Oral
SIM0-010603 inhibited stem cell factor receptor (Kit), vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β), glial cell line-derived neurotrophic factor receptor (Rearranged during Transfection; RET), and Fms-like tyrosine kinase-3 (FLT3) with IC(50) values between 5.0 and 68.1 nmol/l. SIM-010603 exhibited lower activity in regard to proliferation of NCI-H460, MDA-MB-435, and T241-VEGF-A cells (IC(50) > 1 umol/l)
| Substance Class |
Chemical
Created
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admin
on
Edited
Sat Dec 16 11:31:35 UTC 2023
by
admin
on
Sat Dec 16 11:31:35 UTC 2023
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| Record UNII |
H4X2M2NN5N
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| Record Status |
Validated (UNII)
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1032265-57-8
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56935577
Created by
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H4X2M2NN5N
Created by
admin on Sat Dec 16 11:31:35 UTC 2023 , Edited by admin on Sat Dec 16 11:31:35 UTC 2023
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ACTIVE MOIETY |
The No Observed Adverse Effect Level (NOAEL) of SIM010603 was 5mg/kg/day for rats, and undefined for dogs. The treatment resulted in unscheduled mortality in dogs receiving 10mg/kg of SIM010603 or Sunitinib. The adverse effects of SIM010603 on rats and dogs mainly included gastrointestinal toxicity, skeletal toxicity, myelosuppression, thymus atrophy, bronchopneumonia, cardiovascular dysfunction, and pancreatic toxicity.
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