B-Raf kinase inhibitors for cancer treatment.
The Raf-MEK-ERK signaling pathway is critical for cell survival, growth, proliferation and tumorigenesis. Among the three isoforms of Raf protein kinases, in vitro and in vivo studies have shown that B-Raf functions as the primary MEK activator. B-Raf is one of the most frequently mutated genes in human cancers with a high prevalence in melanoma, and many of the B-Raf mutations activate the kinase activity of B-Raf. B-Raf kinase represents an excellent target for anticancer therapy based on preclinical target validation, epidemiology and drugability. Several small-molecule inhibitors of B-Raf kinase are currently undergoing clinical evaluation, with others due to enter clinical development in the near future.
Li
Nanxin
N
Genomics Institute of the Novartis Research Foundation, Kinase Platform, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Batt
David
D
Warmuth
Markus
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010671:Phenylurea Compounds; D011725:Pyridines; C508204:SB-590885; D009536:Niacinamide; D000077157:Sorafenib; D048493:Proto-Oncogene Proteins B-raf