JNJ-38158471 是一种耐受良好，有口服活性的高选择性VEGFR-2抑制剂，IC50值为 40 nM。JNJ-38158471 还抑制Ret和Kit，IC50值分别为 180 和 500 nM。
| 生物活性 | JNJ-38158471 is a well tolerated, orally available, highly selectiveVEGFR-2inhibitor, with anIC50of 40 nM. JNJ-38158471 also inhibitsRetandKitwithIC50s of 180 and 500 nM, respectively[1]. |
| IC50& Target[1] | VEGFR-2 40 nM (IC50) | RET 180 nM (IC50) | c-Kit 500 nM (IC50) |
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体外研究
(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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体内研究
(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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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