az-628 has been researched along with Melanoma* in 1 studies
1 other study(ies) available for az-628 and Melanoma
| Article | Year |
|---|---|
Discovery and optimization of a novel series of potent mutant B-Raf(V600E) selective kinase inhibitors.
B-Raf represents an attractive target for anticancer therapy and the development of small molecule B-Raf inhibitors has delivered new therapies for metastatic melanoma patients. We have discovered a novel class of small molecules that inhibit mutant B-Raf(V600E) kinase activity both in vitro and in vivo. Investigations into the structure-activity relationships of the series are presented along with efforts to improve upon the cellular potency, solubility, and pharmacokinetic profile. Compounds selectively inhibited B-Raf(V600E) in vitro and showed preferential antiproliferative activity in mutant B-Raf(V600E) cell lines and exhibited selectivity in a kinase panel against other kinases. Examples from this series inhibit growth of a B-Raf(V600E) A375 xenograft in vivo at a well-tolerated dose. In addition, aminoquinazolines described herein were shown to display pERK elevation in nonmutant B-Raf cell lines in vitro. Topics: Animals; Humans; Male; Melanoma; Mice; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Quinazolines; Rats; Structure-Activity Relationship | 2013 |