Description
PLX-4720 can inhibit b-Raf(V600E) and c-Raf(V600E) with IC50 of 13 nM and 6.7 nM.
Storage
2 years at -20centigrade Powder
Targets
b-Raf(V600E), c-Raf(V600E)
Molecular Formula
C17H14ClF2N3O3S
Chemical Name
N-(3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide
Solubility
DMSO 83 mg/mL Water
In vitro
PLX-4720 is a B-raf and c-raf inhibitor with IC50 of 13 nM and 6.7 nM. Activating mutations in B-RAF and N-RAS occur in approximately 60 and approximately 15% of melanomas, respectively. The most common mutation in B-RAF is V600E, which activates B-RAF and the downstream MEK-ERK1/2 pathway. Thus, B-RAF(V600E) is a viable therapeutic target. PLX4720 is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma. The effects of PLX4720 across the genotypic spectrum in melanoma remain unclear. PLX4720 treatment rapidly induces hyperactivation of the MEK-ERK1/2 pathway in mutant N-RAS melanoma cells. And PLX4720-induced hyperactivation of the MEK-ERK1/2 pathway promotes resistance to apoptosis in both non-invasive and invasive mutant N-RAS melanoma cells but does not enhance cell cycle properties.
In vivo
Combination of thyroidectomy and PLX4720 can extend survival and would decrease tumor burden in a mouse model. As B-Raf(V600E) is a frequent mutation in anaplastic thyroid cancers and is a novel therapeutic target, it could be an effective therapeutic strategy for early anaplastic thyroid cancers that harbor the B-Raf(V600E) mutation and are refractory to conventional therapeutic modalities.
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