PLX-4720

Description

The Raf kinases activate cellular pathways that lead to cell proliferation and can contribute to certain types of cancer. Mutations in the kinase B-Raf are involved in a wide range of cancers. In particular, the mutation B-Raf^V600E occurs in melanomas and thyroid cancer but is poorly targeted by many inhibitors of wild type B-Raf. PLX4720 is an orally-available, highly selective inhibitor of B-Raf^V600E (IC₅₀ = 13 nM). It is less effective against wild type B-Raf (IC₅₀ = 160 nM) as well as several other kinases. PLX4720 induces cell cycle arrest and apoptosis in cells and xenografts expressing the mutant of B-Raf.

The Uses of PLX-4720

PLX4720 is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma.

The Uses of PLX-4720

Labelled PLX4720. It is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma.

The Uses of PLX-4720

A potent and selective inhibitor of B-RafV600E and c-Raf-1Y340D/Y341D with IC50s of 13 nM and 6.7 nM, respectively.

What are the applications of Application

Raf Kinase Inhibitor V is an inhibitor of Raf kinase

Definition

ChEBI: A pyrrolopyridine that is vemurafenib in which the p-chlorophenyl group has been replaced by chlorine. It is a potent and selective inhibitor of the Raf kinase B-Raf(V600E).

Storage

+4°C

Advantages

PLX4720, a 7-azaindole derivative that inhibits B-RafV600E with an IC50 of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-RafV600E kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-RafV600E-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-RafV600E-positive cells. In B-RafV600E-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity[1].