PLX7904 is a potent and selective BRAF inhibitor, with IC50 of appr 5 nM against BRAFV600E in mutant RAS expressing cells. PLX7904 potently inhibit ERK1/2-driven GAL4-Elk1 reporter activity in PRT cells as well as parental cells. PLX7904 potently inhibits phosphorylation of ERK1/2 in mutant BRAF melanoma cells without eliciting paradoxical activation in wild-type BRAF, mutant NRAS melanoma cells.
In vivo, PLX7904 inhibits the COLO205 xenograft growth in eight mice per group.
|Cell lines||WM793, WM115, WM9, WM278, WM1346, WM1366, WM1361A, Sbcl2, 1205Lu, A375, SK-MEL 24, SKMEL-2, and SK-MEL 207 cells|
|Preparation method||Cells are treated with 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.|
|Concentrations||0, 0.05, 0.1, 1, 5 μM|
|Incubation time||24 h|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO: ≥ 40 mg/mL|
RAF inhibitors that evade paradoxical MAPK pathway activation.
Zhang C, et al. Nature. 2015 Oct 22;526(7574):583-6. PMID: 26466569.
Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors.
Basile KJ, et al. Pigment Cell Melanoma Res. 2014 May;27(3):479-84. PMID: 24422853.
Selective RAF inhibitor impairs ERK1/2 phosphorylation and growth in mutant NRAS, vemurafenib-resistant melanoma cells.
Le K, et al. Pigment Cell Melanoma Res. 2013 Jul;26(4):509-17. PMID: 23490205.
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