Selective B-Raf kinase inhibitor, subject to on-going trials as a small-molecule inhibitor of mutant B-Raf, which is mutated in a number of cancers, and in particular, 70% of malignant melanoma. The V600E mutation which activates the MAPK pathway so promoting cell proliferation and preventing apoptosis is targetted. Its use in treating metastatic malignant melanoma appears promising, including a large trial that was stopped early due to a good early results. FDA approval was gained in August 2011.It is also likely to be effective in hairy cell leukaemia with at least one case report of clinical remission.
- Cutaneous squamous-cell carcinomas (mainly keratoacanthomas develop in about 26%)
- ↑ Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proceedings of the National Academy of Sciences of the United States of America. 2008 Feb 26; 105(8):3041-6.(Link to article – subscription may be required.)
- ↑ Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB. Inhibition of mutated, activated BRAF in metastatic melanoma. The New England journal of medicine. 2010 Aug 26; 363(9):809-19.(Link to article – subscription may be required.)
- ↑ Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. The New England journal of medicine. 2011 Jun 30; 364(26):2507-16.(Link to article – subscription may be required.). See also Clinical Trials information