Dabrafenib

Dabrafenib

Clinical data
Trade names	Tafinlar
License data	EU EMA: by INN
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
KEGG	D10064
ChEBI	CHEBI:75045
ChEMBL	ChEMBL2028663
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
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.

Approvals and indications

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.

Clinical trial data demonstrated that resistance to dabrafenib and other BRAF inhibitors occurs within 6 to 7 months. To overcome this resistance, the BRAF inhibitor dabrafenib was combined with the MEK inhibitor trametinib. On January 8, 2014, the FDA approved this combination of dabrafenib and trametinib for BRAF V600E/K-mutant metastatic melanoma. On May 1, 2018, the FDA approved the combination dabrafenib/trametinib as an adjuvant treatment for BRAF V600E-mutated, stage III melanoma after surgical resection based on the results of the COMBI-AD phase 3 study, making it the first oral chemotherapy regimen that prevents cancer relapse for node positive, BRAF-mutated melanoma.

[April 2017] The European Union approved the combination with trametinib for BRAF V600-positive advanced or metastatic non small-cell lung cancer (NSCLC).

Further reading

U.S. National Center for Biotechnology Information: Medical Genetics Summaries - Dabrafenib Therapy and BRAF and G6PD Genotype

References

Latest research - Dabrafenib

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