Dabrafenib

• CAT Number: I006367
• CAS Number: 1195765-45-7 (free base)
• Molecular Formula: C23H20F3N5O2S2
• Molecular Weight: 519.561
• Purity: ≥95%
• Synonyms: N-(3-(5-(2-aminopyrimidin-4-yl)-2-(tert-butyl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4°C for short term or -20 °C for long term
• IUPAC Name: N-[3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide
• 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)
• InChIKey: BFSMGDJOXZAERB-UHFFFAOYSA-N
• SMILES: CC(C)(C)C1=NC(=C(S1)C2=NC(=NC=C2)N)C3=C(C(=CC=C3)NS(=O)(=O)C4=C(C=CC=C4F)F)F

Dabrafenib, also known as GSK2118436 , is an orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. On May 29, 2013, FDA approved this drug.

Reference

1:Combined dabrafenib and trametinib treatment in a case of chemotherapy-refractory extrahepatic BRAF V600E mutant cholangiocarcinoma: dramatic clinical and radiological response with a confusing synchronic new liver lesion. Kocsis J, Árokszállási A, András C, Balogh I, Béres E, Déri J, Peták I, Jánváry L, Horváth Z.J Gastrointest Oncol. 2017 Apr;8(2):E32-E38. doi: 10.21037/jgo.2017.01.06. PMID: 28480077 Free PMC Article2:Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Long GV, Flaherty KT, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Chiarion-Sileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JBAG, Hansson J, Utikal J, Ferraresi V, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, Davies MA, Lane SR, Legos JJ, Mookerjee B, Grob JJ.Ann Oncol. 2017 May 5. doi: 10.1093/annonc/mdx176. [Epub ahead of print] PMID: 28475671 3:Simple and cost-effective liquid chromatography-mass spectrometry method to measure dabrafenib quantitatively and six metabolites semi-quantitatively in human plasma. Vikingsson S, Dahlberg JO, Hansson J, Höiom V, Gréen H.Anal Bioanal Chem. 2017 Jun;409(15):3749-3756. doi: 10.1007/s00216-017-0316-8. Epub 2017 Apr 20. PMID: 28429064 4:An UPLC-MS/MS method for the quantification of BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (cobimetinib, trametinib, binimetinib) in human plasma. Application to treated melanoma patients. Rousset M, Titier K, Bouchet S, Dutriaux C, Pham-Ledard A, Prey S, Canal-Raffin M, Molimard M.Clin Chim Acta. 2017 Apr 12;470:8-13. doi: 10.1016/j.cca.2017.04.009. [Epub ahead of print] PMID: 28412197 5:Prediction of the Transporter-Mediated Drug-Drug Interaction Potential of Dabrafenib and Its Major Circulating Metabolites. Ellens H, Johnson M, Lawrence SK, Watson C, Chen L, Richards-Peterson LE.Drug Metab Dispos. 2017 Jun;45(6):646-656. doi: 10.1124/dmd.116.073932. Epub 2017 Mar 20. PMID: 28320730 6:Sequential monitoring of pigmented lesions during dabrafenib treatment: a prospective study and a literature overview. Dika E, Lambertini M, Fanti PA, Piraccini BM, Gurioli C, Ravaioli GM, Chessa MA, Traniello Gradassi A, Melotti B, Sperandi F, Patrizi A.G Ital Dermatol Venereol. 2017 Mar 14. doi: 10.23736/S0392-0488.17.05526-2. [Epub ahead of print] PMID: 28290623 7:Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAFV600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Schreuer M, Jansen Y, Planken S, Chevolet I, Seremet T, Kruse V, Neyns B.Lancet Oncol. 2017 Apr;18(4):464-472. doi: 10.1016/S1470-2045(17)30171-7. Epub 2017 Mar 4. PMID: 28268064 8:Dabrafenib plus trametinib rechallenge in four melanoma patients who previously progressed on this combination. Rogiers A, Wolter P, Bechter O.Melanoma Res. 2017 Apr;27(2):164-167. doi: 10.1097/CMR.0000000000000320. PMID: 28252479 9:Anti-inflammatory effects of dabrafenib in vitro and in vivo. Lee IC, Kim J, Bae JS.Can J Physiol Pharmacol. 2017 Feb 3:1-11. doi: 10.1139/cjpp-2016-0519. [Epub ahead of print] PMID: 28177661 10:The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib/dabrafenib-resistant melanoma cells in vitro and in vivo. Booth L, Roberts JL, Sander C, Lee J, Kirkwood JM, Poklepovic A, Dent P.Oncotarget. 2017 Mar 7;8(10):16367-16386. doi: 10.18632/oncotarget.14829. PMID: 28146421 Free PMC Article