Synonym
Dabrafenib mesylate; GSK 2118436B; GSK2118436B; GSK-2118436B; GSK2118436 Methane sulfonate salt; Taflinar.
IUPAC/Chemical Name
N-(3-(5-(2-aminopyrimidin-4-yl)-2-(tert-butyl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide methanesulfonate
InChi Key
YKGMKSIHIVVYKY-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H20F3N5O2S2.CH4O3S/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;1-5(2,3)4/h4-11,31H,1-3H3,(H2,27,28,29);1H3,(H,2,3,4)
SMILES Code
O=S(C1=C(F)C=CC=C1F)(NC2=CC=CC(C3=C(C4=NC(N)=NC=C4)SC(C(C)(C)C)=N3)=C2F)=O.CS(=O)(O)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Dabrafenib mesylate is a white to slightly colored solid with three pKas: 6.6, 2.2, and -1.5. It is very slightly soluble at pH 1 and practically insoluble above pH 4 in aqueous media.
Biological target:
Dabrafenib Mesylate is a Raf kinase inhibitor with IC50s of 0.6 and 5.0 nM for RafV600E and c-Raf, respectively.
In vitro activity:
The anti-inflammatory activities of DAB (Dabrafenib) were determined by measuring permeability, neutrophils adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs). DAB inhibited LPS (lipopolysaccharide) induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion and transendothelial migration of neutrophils to human endothelial cells. Furthermore, DAB suppressed the production of tumor necrosis factor-α (TNF-α) or interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS.
Reference: Can J Physiol Pharmacol. 2017 Jun;95(6):697-707. https://cdnsciencepub.com/doi/10.1139/cjpp-2016-0519?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
In vivo activity:
The effect of DAB in the prevention or treatment of renal IRI (ischemia-reperfusion injury) was evaluated. In mice, DAB pretreatment improved renal function and also reduced histological injury, inflammation, cell death, and expression of necroptosis-associated proteins. These in vivo experiments indicated that DAB appears to alleviate renal IRI by suppressing cell death and inhibiting inflammatory responses.
Reference: Biochem Biophys Res Commun. 2020 Feb 5;522(2):395-401. https://www.sciencedirect.com/science/article/abs/pii/S0006291X19322314?via%3Dihub
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
55.6 |
90.29 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
615.66
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Liu SS, Chen YY, Wang SX, Yu Q. Protective effect of dabrafenib on renal ischemia-reperfusion injury in vivo and in vitro. Biochem Biophys Res Commun. 2020 Feb 5;522(2):395-401. doi: 10.1016/j.bbrc.2019.11.105. Epub 2019 Nov 23. PMID: 31771879.
2. Lee IC, Kim J, Bae JS. Anti-inflammatory effects of dabrafenib in vitro and in vivo. Can J Physiol Pharmacol. 2017 Jun;95(6):697-707. doi: 10.1139/cjpp-2016-0519. Epub 2017 Feb 3. PMID: 28177661.
In vitro protocol:
1. Liu SS, Chen YY, Wang SX, Yu Q. Protective effect of dabrafenib on renal ischemia-reperfusion injury in vivo and in vitro. Biochem Biophys Res Commun. 2020 Feb 5;522(2):395-401. doi: 10.1016/j.bbrc.2019.11.105. Epub 2019 Nov 23. PMID: 31771879.
2. Lee IC, Kim J, Bae JS. Anti-inflammatory effects of dabrafenib in vitro and in vivo. Can J Physiol Pharmacol. 2017 Jun;95(6):697-707. doi: 10.1139/cjpp-2016-0519. Epub 2017 Feb 3. PMID: 28177661.
In vivo protocol:
1. Liu SS, Chen YY, Wang SX, Yu Q. Protective effect of dabrafenib on renal ischemia-reperfusion injury in vivo and in vitro. Biochem Biophys Res Commun. 2020 Feb 5;522(2):395-401. doi: 10.1016/j.bbrc.2019.11.105. Epub 2019 Nov 23. PMID: 31771879.
2. Lee IC, Kim J, Bae JS. Anti-inflammatory effects of dabrafenib in vitro and in vivo. Can J Physiol Pharmacol. 2017 Jun;95(6):697-707. doi: 10.1139/cjpp-2016-0519. Epub 2017 Feb 3. PMID: 28177661.
1: Banzi M, De Blasio S, Lallas A, Longo C, Moscarella E, Alfano R, Argenziano G. Dabrafenib: a new opportunity for the treatment of BRAF V600-positive melanoma. Onco Targets Ther. 2016 May 6;9:2725-33. doi: 10.2147/OTT.S75104. eCollection 2016. Review. PubMed PMID: 27226731; PubMed Central PMCID: PMC4866744.
2: Spain L, Julve M, Larkin J. Combination dabrafenib and trametinib in the management of advanced melanoma with BRAFV600 mutations. Expert Opin Pharmacother. 2016;17(7):1031-8. doi: 10.1517/14656566.2016.1168805. Epub 2016 Apr 12. Review. PubMed PMID: 27027150.
3: Zia Y, Chen L, Daud A. Future of combination therapy with dabrafenib and trametinib in metastatic melanoma. Expert Opin Pharmacother. 2015;16(14):2257-63. doi: 10.1517/14656566.2015.1085509. Epub 2015 Sep 2. Review. PubMed PMID: 26331795.
4: Giurcaneanu C, Nitipir C, Popa LG, Forsea AM, Popescu I, Bumbacea RS. Evolution of melanocytic nevi under vemurafenib, followed by combination therapy with dabrafenib and trametinib for metastatic melanoma. Acta Dermatovenerol Croat. 2015;23(2):114-21. Review. PubMed PMID: 26228819.
5: Khoja L, Hogg D. Dabrafenib in the treatment of metastatic or unresectable melanoma. Expert Rev Anticancer Ther. 2015 Mar;15(3):265-76. doi: 10.1586/14737140.2015.1014343. Review. PubMed PMID: 25711514.
6: Awad MM, Sullivan RJ. Dabrafenib in combination with trametinib for the treatment of metastatic melanoma. Expert Rev Clin Pharmacol. 2015 Jan;8(1):25-33. doi: 10.1586/17512433.2015.974556. Epub 2014 Dec 4. Review. PubMed PMID: 25473943.
7: McGettigan S. Dabrafenib: A New Therapy for Use in BRAF-Mutated Metastatic Melanoma. J Adv Pract Oncol. 2014 May;5(3):211-5. Review. PubMed PMID: 25089220; PubMed Central PMCID: PMC4114496.
8: Luke JJ, Ott PA. New developments in the treatment of metastatic melanoma - role of dabrafenib-trametinib combination therapy. Drug Healthc Patient Saf. 2014 Jun 24;6:77-88. doi: 10.2147/DHPS.S39568. eCollection 2014. Review. PubMed PMID: 25018652; PubMed Central PMCID: PMC4075957.
9: Rutkowski P, Blank C. Dabrafenib for the treatment of BRAF V600-positive melanoma: a safety evaluation. Expert Opin Drug Saf. 2014 Sep;13(9):1249-58. doi: 10.1517/14740338.2014.939954. Epub 2014 Jul 11. Review. PubMed PMID: 25014231.
10: Kainthla R, Kim KB, Falchook GS. Dabrafenib. Recent Results Cancer Res. 2014;201:227-40. doi: 10.1007/978-3-642-54490-3_14. Review. PubMed PMID: 24756796.
11: Kainthla R, Kim KB, Falchook GS. Dabrafenib for treatment of BRAF-mutant melanoma. Pharmgenomics Pers Med. 2013 Dec 31;7:21-9. doi: 10.2147/PGPM.S37220. eCollection 2014. Review. PubMed PMID: 24516336; PubMed Central PMCID: PMC3917541.
12: Trinh VA, Davis JE, Anderson JE, Kim KB. Dabrafenib therapy for advanced melanoma. Ann Pharmacother. 2014 Apr;48(4):519-29. doi: 10.1177/1060028013513009. Epub 2013 Nov 20. Review. PubMed PMID: 24259661.
13: Medina T, Amaria MN, Jimeno A. Dabrafenib in the treatment of advanced melanoma. Drugs Today (Barc). 2013 Jun;49(6):377-85. doi: 10.1358/dot.2013.49.6.1968669. Review. PubMed PMID: 23807941.
14: Luke JJ, Hodi FS. Ipilimumab, vemurafenib, dabrafenib, and trametinib: synergistic competitors in the clinical management of BRAF mutant malignant melanoma. Oncologist. 2013 Jun;18(6):717-25. doi: 10.1634/theoncologist.2012-0391. Epub 2013 May 24. Review. PubMed PMID: 23709751; PubMed Central PMCID: PMC4063399.
15: Gibney GT, Zager JS. Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies. Expert Opin Drug Metab Toxicol. 2013 Jul;9(7):893-9. doi: 10.1517/17425255.2013.794220. Epub 2013 Apr 29. Review. PubMed PMID: 23621583.
16: Menzies AM, Long GV, Murali R. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012;6:391-405. doi: 10.2147/DDDT.S38998. Epub 2012 Dec 11. Review. PubMed PMID: 23251089; PubMed Central PMCID: PMC3523565.
17: Heneberg P. [Dabrafenib: the new inhibitor of hyperactive B-RAF kinase]. Klin Onkol. 2012;25(5):333-9. Review. Czech. PubMed PMID: 23102194.
