Dabrafenib

Dabrafenib
Clinical data
Trade names	Tafinlar
ATC code	L01XE23 (WHO) ;
Legal status
Legal status	US: ℞-only;
Identifiers
	IUPAC name N-{3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide;
CAS Number	1195765-45-7;
PubChem CID	44462760;
ChemSpider	25948204;
ChEBI	CHEBI:75045;
ChEMBL	ChEMBL2028663;
CompTox Dashboard (EPA)	DTXSID20152499 ;
ECHA InfoCard	100.215.965
Chemical and physical data
Formula	C23H20F3N5O2S2
Molar mass	519.56 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)(C)c1nc(c(s1)c2ccnc(n2)N)c3cccc(c3F)NS(=O)(=O)c4c(cccc4F)F;
	InChI InChI=1S/C23H20F3N5O2S2/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25/h4-11,31H,1-3H3,(H2,27,28,29); Key:BFSMGDJOXZAERB-UHFFFAOYSA-N;

Dabrafenib (trade name Tafinlar, GSK2118436) is a drug for the treatment of cancers associated with a mutated version of the gene BRAF. Dabrafenib acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth. Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma.^[1]^[2]

The Food and Drug Administration initially approved dabrafenib as a single agent treatment for patients with BRAF V600E mutation-positive advanced melanoma on May 30, 2013.^[3] Clinical trial data demonstrated that resistance to dabrafinib and other BRAF inhibitors occurs within 6 to 7 months.^[4] To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib.^[4] On January 8, 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma.^[5]^[6]

References

^ Gibney, G. T.; Zager, J. S. (2013). "Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies". Expert Opinion on Drug Metabolism & Toxicology. 9 (7): 1. doi:10.1517/17425255.2013.794220. PMID 23621583.
^ Huang, T.; Karsy, M.; Zhuge, J.; Zhong, M.; Liu, D. (2013). "B-Raf and the inhibitors: From bench to bedside". Journal of Hematology & Oncology. 6: 30. doi:10.1186/1756-8722-6-30. PMC 3646677. PMID 23617957.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013.
^ ^a ^b "Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations". 367 (18). New England Journal of Medicine. November 1, 2012: 1694–703. doi:10.1056/NEJMoa1210093. PMC 3549295. PMID 23020132. {{cite journal}}: Cite journal requires |journal= (help)
^ "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive. January 9, 2013.
^ Maverakis E; Cornelius LA; Bowen GM; Phan T; Patel FB; Fitzmaurice S; He Y; Burrall B; Duong C; Kloxin AM; Sultani H; Wilken R; Martinez SR; Patel F (2015). "Metastatic melanoma - a review of current and future treatment options". Acta Derm Venereol. 95 (5): 516–524. doi:10.2340/00015555-2035. PMID 25520039.

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[1] Gibney, G. T.; Zager, J. S. (2013). "Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies". Expert Opinion on Drug Metabolism & Toxicology. 9 (7): 1. doi:10.1517/17425255.2013.794220. PMID 23621583.

[2] Huang, T.; Karsy, M.; Zhuge, J.; Zhong, M.; Liu, D. (2013). "B-Raf and the inhibitors: From bench to bedside". Journal of Hematology & Oncology. 6: 30. doi:10.1186/1756-8722-6-30. PMC 3646677. PMID 23617957.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[3] "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013.

[NEJM-4] "Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations". 367 (18). New England Journal of Medicine. November 1, 2012: 1694–703. doi:10.1056/NEJMoa1210093. PMC 3549295. PMID 23020132. {{cite journal}}: Cite journal requires |journal= (help)

[5] "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive. January 9, 2013.

[6] Maverakis E; Cornelius LA; Bowen GM; Phan T; Patel FB; Fitzmaurice S; He Y; Burrall B; Duong C; Kloxin AM; Sultani H; Wilken R; Martinez SR; Patel F (2015). "Metastatic melanoma - a review of current and future treatment options". Acta Derm Venereol. 95 (5): 516–524. doi:10.2340/00015555-2035. PMID 25520039.

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