PLX7904 is a potent and selective BRAF inhibitor, with IC₅₀ of appr 5 nM against BRAF in mutant RAS expressing cells.

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PLX7904 inhibits the 体外研究 growth of two melanoma cell lines (A375 and COLO829) and an additional human colorectal cancer cell line COLO205 that expresses BRAF with IC₅₀ values of 0.17 μM, 0.53 μM, and 0.16 μM, respectively, on a par with vemurafenib IC₅₀ values in the same assays (0.33 μM, 0.69 μM, and 0.25 μM, respectively). PLX7904 and PLX8394 potently inhibit ERK1/2-driven GAL4-Elk1 reporter activity in PRT cells as well as parental cells. PLX7904 and PLX8394 treatment at 1 μM concentration reduce colony formation and viability in parental cells to a similar level as PLX4720. PPLX7904 potently inhibits phosphorylation of ERK1/2 in mutant BRAF melanoma cells without eliciting paradoxical activation in wild-type BRAF, mutant NRAS melanoma cells. PPLX7904 inhibits ERK1/2 in PLX470-resistant cell lines. PPLX7904 treatment promotes apoptosis and inhibits anchorage-independent growth of vemurafenib resistant cells.

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• [1]. Zhang C, et al. RAF inhibitors that evade paradoxical MAPK pathway activation. Nature. 2015 Oct 22;526(7574):583-586.  [Information]

  [2]. Basile KJ, et al. Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors. Pigment Cell Melanoma Res. 2014 May;27(3):479-84  [Information]

  [3]. Le K, et al. Selective RAF inhibitor impairs ERK1/2 phosphorylation and growth in mutant NRAS, vemurafenib-resistant melanoma cells. Pigment Cell Melanoma Res. 2013 Jul;26(4):509-17  [Information]

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