Description
As an oncogenic BRAF kinase inhibitor, PLX4032 (Vemurafenib) can inhibit B-RAF(V600E), C-RAF, MAP4K5 (KHS1), SRMS, ACK1 and FGR with IC50 of 31 nM, 48 nM, 51 nM, 18 nM, 19 nM and 63 nM.
Storage
2 years at -20 centigrade
Targets
b-Raf(V600E)/c-Raf, MAP4K5KHS1), SRMS, ACK1, FGR
Molecular Formula
C23H18ClF2N3O3S
Solubility
DSMO 98 mg/mL Water
In vitro
As an oncogenic BRAF kinase inhibitor, PLX4032 (Vemurafenib) can inhibit B-RAF(V600E), C-RAF, MAP4K5 (KHS1), SRMS, ACK1 and FGR with IC50 of 31 nM, 48 nM, 51 nM, 18 nM, 19 nM and 63 nM. For cell lines PLX4032 can inhibit human PBMC with IC50 between 50 nM and 150 nM, while PLX4032 inhibit BRAF(V600E) mutant melanoma cell lines with IC50 of 1 uM. PLX4032 had a marginal effect on cell-cycle arrest, apoptotic cell changes or alteration of phosphorylated signaling molecules in lymphocytes. The cytotoxic activity of PLX4032 was maintained up to high concentrations of 50 uM. PLX4032 inhibits the proliferation of BRAF(V600E) tumor cells but not that of HER kinase-dependent tumors. PLX4032 inhibits ERK signaling output in mutant BRAF cells, whereas it transiently activates the expression of these genes in tumor cells with wild-type RAF. Thus, PLX4032 inhibits ERK signaling output in a mutant BRAF-selective manner. RG7204 potently inhibited proliferation and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase and ERK phosphorylation in a panel of tumor cell lines, including melanoma cell lines expressing BRAF(V600E) or other mutant BRAF proteins altered at codon 600, but, RG7204 lacked activity in cell lines that express wild-type BRAF or non-V600 mutations.
In vivo
In several tumor xenograft models of BRAF(V600E)-expressing melanoma, PLX4032(RG7204) treatment caused partial or complete tumor regressions and improved animal survival, in a dose-dependent manner.
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