CS-2660

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CS-2660是一种高选择性、口服、耐受性良好的VEGFR2抑制剂，IC50为40 nM，抑制密切相关的酪氨酸激酶，例如Ret和Kit，IC50为180 nM和500 nM。

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.

JNJ-38158471 (1-500 nM; 1 hour) inhibits VEGF-stimulated VEGFR-2 autophosphorylation in HUVECs.JNJ-38158471 (50-1000 nM; 12-16 hours) signi?cantly 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 phospoho-VEGFR2 levels at 95, 88, 77 and 73% with the concentration of 500, 100, 10 and 1 nM, respectively.

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 control animals.JNJ-38158471 (100 mg/kg; p.o.; once-daily) treatment shows statistically signi?cant activity compare with vehicle treat 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 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 ef?cacy with the dose from 100 to 200 mg/kg daily.Animal Model:Female athymic nude mice; 5-6 weeks; implanted subcutaneously human skin melanoma cells (A375)Dosage:100 mg/kg Administration:Once-daily oral administration for 28 days Result:Inhibited 90% growth of tumor 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.

JNJ-38158471

Angiogenesis

c-Kit

Kit|Ret|VEGFR2

——

——

951151-97-6

364.79

C15H17ClN6O3

>98% (HPLC)

DMSO:30 mg/ml (82.24 mM)

CCNC(=O)NC1=C(C=C(C=C1)OC2=NC=NC(=C2/C=N/OC)N)Cl

——

(-20℃)

With Ice Pack

≥ 2 years