Vemurafenib (PLX4032, RG7204)是一种新型有效的B-RafV600E抑制剂，无细胞试验中IC50为31 nM。

≥98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

维罗非尼；PLX-4032; RG7204; R7204; RO5185426; Vemurafenib

白色粉末

DMSO ：90 mg/mL (183.7 mM)

SRMS ,ACK1 ,B-Raf (V600E) ,C-Raf ,MAP4K5 (KHS1)

PLX4032 inhibits B-RAFV600E, C-RAF, as well as wildtype B-RAF, with IC50 of 31 nM, 48 nM and 100 nM, respectively. PLX4032 also inhibits several non-RAF kinases, including ACK1, KHS1, and SRMS, with IC50 of 18 nM to 51 nM. In melanoma cell lines, the inhibitory effect by PLX4032 depends on B-RAF mutational status, because PLX4032 potently inhibits those harboring B-RAF V600 mutants, including V600E, V600D, V600K, and V600R, but not wildtype or other mutants. The IC50 values of PLX4032 on these cells, including MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058, ranges from 20 nM to 1 μM. In these cells, PLX4032 (0.1 μM to 30 μM) also inhibits the phosphorylation of both MEK1/2 and ERK1/2. PLX4032 is highly effective in the treatment of melanoma, for its ability of inhibiting B-RAFV600E. However, PLX4032 displays limited effect in colon cancer patients that also carrying B-RAFV600E oncoprotein. The reason for this is that, in colon cancer cells, B-RAFV600E inhibition by PLX4032 results in a rapid feedback EGFR activation, which compensates for the PLX4032-inhibited cell proliferation.

In B-RAFV600E-mutant mice xenograft models, PLX4032 (6 mg/kg–20 mg/kg) inhibits tumor growth. In mice xenograft models of LOX, Colo829, and A375 cells, PLX4032 (12.5 mg/kg–100 mg/kg) inhibits tumor growth and prolongs mice survival.

[1] Bollag G, et al. Nature, 2010, 467(7315), 596-599.

[2] Yang H, et al. Cancer Res, 2010, 70(13), 5518-5527.

[3] Prahallad A, et al. Nature, 2012, 483(7387), 100-103.

[4] Kumar A, et al. J Mol Biol, 2005, 348(1), 183-193.

[5] Yang H, et al. Cancer Res, 2012, 72(3), 779-789.