PLX4032, also known as Vemurafenib, RG7204, RO5185426 and Zelboraf, is a highly selective B-Raf enzyme inhibitor with an IC50 of 44 nM against V600E-mutant BRAF.
|Cell lines||MDA-MB-435 cells line|
|Preparation method||Cellular proliferation assays Cellular proliferation was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT; Sigma) assay. Briefly, cells were plated in 96-well microtiter plates at a density of 1,000 to 5,000 cells per well in a volume of 180 μL. For the assay, RG7204 was prepared at 10 times the final assay concentration in media containing 1% DMSO. Twenty-four hours after cell plating, 20 μL of the appropriate dilution were added to plates in duplicate. The plates were assayed for proliferation 6 days after the cells were plated according to the procedure originally described by Mosmann . The IC50 was determined from the regression of a plot of the logarithm of the concentration versus percent inhibition by XLfit (version 4.2; IDBS) using the Dose-Response One-Site Model (#205).|
|Incubation time||6 days|
|Animal models||Colo829 and A375 xenografts|
|Formulation||an aqueous vehicle containing 2% Klucel LF (Hydroxypropylcellulose; Aqualon) and adjusted to pH 4 with dilute HCl.|
|Dosages||100 mg/kg bid|
|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.
|Source||Cell Death Differ (2016). Figure 2. PLX4032|
|Cell Lines||BRAF mutant melanoma cell lines|
|Incubation Time||24 h|
|Results||PLX4032-induced upregulation of BIM and PUMA occurred normally in the control sgRNA transduced cell lines.|
|Source||Cell Death Differ (2016). Figure 1. PLX4032|
|Cell Lines||BRAFWT cells|
|Concentrations||0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM|
|Incubation Time||24 h|
|Results||We found that PLX4032 induced significant dose-dependent apoptosis over a time course of 5 days in all BRAF mutant melanoma cell lines (M14, UACC257, Malme3M, SKMEL5 and UACC62), whereas the BRAFWT cells (CHL-1) were unaffected.|
BH3-only protein silencing contributes to acquired resistance to PLX4720 in human melanoma.
Shao Y et al. Cell Death Differ. 2012 Aug 3. PMID: 22858545.
Vemurafenib (RG67204, PLX4032): a potent, selective BRAF kinase inhibitor.
Patrawala S et al. Future Oncol. 2012 May;8(5):509-23. PMID: 22646766.
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