AI Article Synopsis
- B-Raf(V600E) mutation leads to overactive MAP kinase signaling in various tumors, particularly melanomas.* -
- GSK2118436 is a selective inhibitor that effectively targets Raf kinases, showing strong anti-cancer effects in lab tests and mouse models of melanoma.* -
- Early clinical trials indicate that GSK2118436 demonstrates significant effectiveness in patients with melanoma that have the B-Raf mutation.*
Article Abstract
Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-Raf(V600E) mutated enzyme has been observed in a number of human tumors, including melanomas. Herein we report the discovery and biological evaluation of GSK2118436, a selective inhibitor of Raf kinases with potent in vitro activity in oncogenic B-Raf-driven melanoma and colorectal carcinoma cells and robust in vivo antitumor and pharmacodynamic activity in mouse models of B-Raf(V600E) human melanoma. GSK2118436 was identified as a development candidate, and early clinical results have shown significant activity in patients with B-Raf mutant melanoma.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027516 | PMC |
| http://dx.doi.org/10.1021/ml4000063 | DOI Listing |
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