Dabrafenib

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Dabrafenib
Dabrafenib.svg
Clinical data
Trade names Tafinlar
Pregnancy
category
  • US: D (Evidence of risk)
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.215.965
Chemical and physical data
Formula C23H20F3N5O2S2
Molar mass 519.56 g/mol
3D model (JSmol)

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]

Approvals and indications[edit]

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]

[April 2017] The European Union approved the combination with trametinib for BRAF V600-positive advanced or metastatic non small-cell lung cancer (NSCLC).[7]

References[edit]

  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. PMID 23621583. doi:10.1517/17425255.2013.794220. 
  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. PMC 3646677Freely accessible. PMID 23617957. doi:10.1186/1756-8722-6-30. 
  3. ^ "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013. 
  4. ^ 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. PMC 3549295Freely accessible. PMID 23020132. doi:10.1056/NEJMoa1210093. 
  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. PMID 25520039. doi:10.2340/00015555-2035. 
  7. ^ Dabrafenib/Trametinib Combo Wins EU Approval for BRAF+ NSCLC. April 2017