Inhibitors bind and inhibit highly active BRAF mutants

Stable Identifier
R-HSA-6802938
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Inhibitors bind and inhibit highly active BRAF mutants
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The class I ATP competitive inhibitors vemurafenib and dabrafenib have been approved for treatment of V600E melanoma, and other BRAF-selective inhibitors are in clinical and preclinical trials. These inhibitors bind to the active conformation of the enzyme promoted by the V600E mutation (King et al, 2006; Tsai et al, 2008).

Literature References
PubMed ID Title Journal Year
17145850 Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885

Luo, L, Kumar, R, Wilson, DM, Morrissey, MM, Lougheed, JC, Batorsky, RS, Adams, JL, Lakdawala, AS, May, EW, Takle, AK, Zhang, SY, Rusnak, DW, Karreth, F, Smalley, KS, Do, HT, Rominger, CM, Patrick, DR, Huang, PS, Lee, J, Contractor, RG, Wang, L, Hugger, E, Schaber, MD, Chau, D, Stout, TJ, King, AJ, Ho, ML, Herlyn, M, Tuveson, DA

Cancer Res. 2006
18287029 Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity

Lee, JT, Kim, SH, Habets, G, Marimuthu, A, Luu, C, Rice, J, West, BL, Schlessinger, J, Nguyen, H, Bremer, R, Suzuki, Y, Cantwell, J, Fong, D, Wang, W, Tsai, J, Lam, B, Hirth, P, Zhang, KY, Zhu, YL, Zhang, J, Ibrahim, PN, Shellooe, R, Zhang, C, Powell, B, Haass, NK, Cho, H, Sproesser, K, Li, L, Smalley, KS, Artis, DR, Kong, J, Herlyn, M, Gillette, S, Cheung, I, Bollag, G, Settachatgul, C, Liu, J, Mamo, S

Proc. Natl. Acad. Sci. U.S.A. 2008
Participants
Input
Output
Participates
as an event of
Functional status

Gain of function of high kinase activity BRAF mutants [cytosol]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cardiofaciocutaneous syndrome DOID:0060233 CFC syndrome, cardio-facial-cutaneous syndrome
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2015-05-18)
Reviewed
Stephens, RM  (2016-08-05)
Created
Rothfels, K  (2015-10-02)
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