| Description |
JNJ-38158471 is a well tolerated, orally available, highly selective VEGFR-2 inhibitor, with an IC50 of 40 nM. JNJ-38158471 also inhibits Ret and Kit with the IC50s of 180 and 500 nM, respectively[1].
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| Related Catalog |
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| Target |
VEGFR-2:40 nM (IC50)
RET:180 nM (IC50)
c-Kit:500 nM (IC50)
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| In Vitro |
JNJ-38158471 (1-500 nM; 1 hour) inhibits VEGF-stimulated VEGFR-2 autophosphorylation in HUVECs[1]. 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[1]. Western Blot Analysis[1] 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.
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| In Vivo |
JNJ-38158471 (10 or 100 mg/kg; p.o.; once-daily) inhibits VEGF-induced corneal neovascularization[1]. 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[1]. JNJ-38158471 (100 mg/kg; p.o.; once-daily) treatment shows statistically significant activity compare with vehicle treat animals. The body weights of both JNJ-38158471-treated and vehicle-treated groups were comparable at study end[1]. Animal Model: Female C57BL/6J mice are implanted with rhVEGF165[1] 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)[1] Dosage: 10, 50, 100, 200 mg/kg Administration: Oral administration for 35 days Result: Achieved optimum efficacy 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)[1] 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[1] Dosage: 100 mg/kg Administration: Once-daily oral administration for two weeks Result: Inhibited polyp formation in the transgenic APC min-mouse model.
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| References |
[1]. Kenneth RL, et, al. A Highly Selective, Orally Bioavailable, Vascular Endothelial Growth Factor receptor-2 Tyrosine Kinase Inhibitor Has Potent Activity in Vitro and in Vivo. Angiogenesis. 2009; 12(3): 287-96.
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