CS-2660

SKU: orb1217438

Description

CS-2660, a highly selective, orally available, well tolerated VEGFR2 inhibitor with IC50 of 40 nM, inhibits closely related tyrosine kinases such as Ret and Kit with IC50 of 180 nM and 500 nM.

Key Properties

• CAS Number: 951151-97-6
• MW: 364.79
• Purity: >98% (HPLC)
• Formula: C₁₅H₁₇ClN₆O₃
• SMILES: CCNC(=O)NC1=C(C=C(C=C1)OC2=NC=NC(=C2/C=N/OC)N)Cl
• Target: c-Kit
• Solubility: DMSO:30 mg/ml (82.24 mM)

Bioactivity

• In Vivo:
  JNJ-38158471 (10 or 100 mg/kg; p.o. ; once daily) inhibits VEGF-induced corneal neovascularization. JNJ-38158471 (10-200 mg/kg; p.o.) inhibits the growth of human tumor xenografts in a dose-dependent manner in both A431 and HCT116 models. JNJ-38158471 treatment is well tolerated, following continuous administration for 24 days, body weights were comparable with those of control animals. JNJ-38158471 (100 mg/kg; p.o. ; once daily) treatment shows statistically significant activity compared with vehicle-treated animals. The body weights of both JNJ-38158471-treated and vehicle-treated groups were comparable at study end. Animal model: Female C57BL/6J mice are implanted with rhVEGF165. Dosage: 10 or 100 mg/kg. Administration: Daily oral administration for 6 days. Result: Caused a marked and apparently dose-dependent inhibition of VEGF-dependent blood vessel formation (100 mg/kg, resulted in 83% inhibition; 10 mg/kg, resulted in 15% inhibition). Animal model: Female athymic nude mice; 5-6 weeks; implanted subcutaneously with human colorectal carcinoma cells (HCT116) or human epidermoid carcinoma cells (A431). Dosage: 10, 50, 100, 200 mg/kg. Administration: Oral administration for 35 days. Result: Achieved optimum efficacy with doses from 100 to 200 mg/kg daily. Animal model: Female athymic nude mice; 5-6 weeks; implanted subcutaneously with human skin melanoma cells (A375). Dosage: 100 mg/kg. Administration: once daily oral administration for 28 days. Result: Inhibited tumor growth by 90% with daily doses of 100 mg/kg. Animal model: Female C57BL/6J-APC Min mice; 5 weeks of age. Dosage: 100 mg/kg. Administration: once daily oral administration for two weeks. Result: Inhibited polyp formation in the transgenic APC Min mouse model.
• In Vitro:
  JNJ-38158471 (1-500 nM; 1 hour) inhibits VEGF-stimulated VEGFR-2 autophosphorylation in HUVECs. JNJ-38158471 (50-1000 nM; 12-16 hours) significantly inhibits VEGF-dependent HUVEC migration. Cellular toxicity is not observed following JNJ-38158471 treatment of HUVECs. Western blot analysis. Cell line: Human umbilical vein endothelial cells (HUVECs). Concentration: 1, 10, 100, 500 nM. Incubation time: 1 hour. Result: Reduced phospho-VEGFR2 levels to 95%, 88%, 77%, and 73% at concentrations of 500, 100, 10 and 1 nM, respectively.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

JNJ-38158471

Quick Database Links

Gene Symbol

c-Kit