PLX7904 是一种有效且选择性的悖论破坏剂 Raf 抑制剂，可抑制突变 BRaf 黑色素瘤细胞中 ERK1/2 的激活。在表达突变体 Ras 的细胞中，对 BRafV600E的IC50值约为 5 nM。

PLX7904, also known as PB04, is a potent and selective paradox-breaker RAF inhibitor. It is able to efficiently inhibit activation of ERK1/2 in mutant BRAF melanoma cells but does not hyperactivate ERK1/2 in mutant RAS-expressing cells.

PLX7940 is able to efficiently inhibit activation of ERK1/2 in mutant BRAF melanoma cells but does not hyperactivate ERK1/2 in mutant RAS-expressing cells. Consistent with ERK1/2 re-activation driving the re-acquisition of malignant properties, PLX7904 promotes apoptosis and inhibits entry into S phase and anchorage-independent growth in mutant N-RAS mediated vemurafenib-resistant cells. PLX7904 is also evaluated in the human SCC cell line A431 and the human breast adenocarcinoma cell line SKBR3 as these cells achieve MAPK pathway activation by upstream signals feeding into RAS (through overexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), respectively)[1][2].

PLX7904 inhibits the COLO205 xenograft growth in eight mice per group[1].

Cells are treated with PB04(PLX7904) at different concentrations (0, 0.05, 0.1, 1, 5 μM) for 24 h. Cells are lysed and analyzed by Western blotting with phospho-MEK1/2, total MEK1/2, phospho-ERK1/2 and total ERK1/2 antibodies. (Only for Reference)

1393465-84-3

C24H22F2N6O3S

512.54

PB04

Ethanol:<1 mgml
H2O:<1 mgml
DMSO:100 mg/mL (195.11 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years