Dabrafenib Mesylate

Catalog No.S5069 Synonyms: GSK2118436 Mesylate

For research use only.

Dabrafenib Mesylate (GSK2118436) is the mesylate salt form of dabrafenib, an orally bioavailable inhibitor of B-raf (BRAF) protein with IC50s of 0.8 nM, 3.2 nM and 5 nM for B-Raf (V600E), B-Raf (WT) and C-Raf, respectively.

Dabrafenib Mesylate Chemical Structure

CAS No. 1195768-06-9

Selleck's Dabrafenib Mesylate has been cited by 58 publications

Purity & Quality Control

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Biological Activity

Description Dabrafenib Mesylate (GSK2118436) is the mesylate salt form of dabrafenib, an orally bioavailable inhibitor of B-raf (BRAF) protein with IC50s of 0.8 nM, 3.2 nM and 5 nM for B-Raf (V600E), B-Raf (WT) and C-Raf, respectively.
Targets
B-Raf (V600E) [1]
(Cell-free assay)
B-Raf [1]
(Cell-free assay)
C-Raf [1]
(Cell-free assay)
0.7 nM 5.2 nM 6.3 nM
In vitro

Dabrafenib displayed compelling inhibitory activity in enzyme and cellular mechanistic assays, and in cell proliferation assays in B-RafV600E-driven melanoma lines, SKMEL28 and A375P F11 (IC50 = 3 and 8 nM, respectively), and colorectal carcinoma line Colo205 (IC50 = 7 nM). Dabrafenib has a minimal effect in vitro on cells with wild-type B-Raf (HFF IC50 = 3.0 μM) and in tumor cells not harboring the activating B-RafV600E mutation. It is highly selective, exhibiting >500-fold selectivity for B-RafV600E compared to most kinases screened. Significant activity (<100-fold selectivity) was observed for a single kinase in the panel, Alk5. GSK2118436 is significantly less effective at inhibiting SMAD2/3 phosphorylation (IC50 = 3.7 μM) compared with inhibiting ERK phosphorylation (IC50 = 4 nM) in a cellular context[1]. Cellular inhibition of BRAFV600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death[2].

Assay
Methods Test Index PMID
Western blot β-catenin ; p-S6 / p-AKT308 / p-AKT473 ; pMEK / pERK / ERK 29167314 24735930 31158244
Growth inhibition assay IC50 24735930
In vivo In a BRAFV600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. Dabrafenib is orally bioavailable, doesn’t significantly accumulate after multiple dosing, and causes a reduction of pERK that is sustained for up to 18 h post-dosing after 7 and 14 days of dosing[2].

Protocol (from reference)

Cell Research:

[2]

  • Cell lines: A375P cells
  • Concentrations: 8 nM
  • Incubation Time: 1 h
  • Method:

    A375P cells were transfected with the indicated siRNA for 72 h and treated with 8 nM dabrafenib (+) or DMSO control (−) for 1 h. Lysates were immunoblotted.

Animal Research:

[1]

  • Animal Models: CD1 nu/nu mice bearing A375P F11 (B-RafV600E) tumors
  • Dosages: 0.1, 1, 10, and 100 mg/kg
  • Administration: oral

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(162.42 mM)
Ethanol 5 mg/mL
(8.12 mM)
Water Insoluble

Chemical Information

Molecular Weight 615.67
Formula

C23H20F3N5O2S2.CH4O3S

CAS No. 1195768-06-9
Storage 3 years -20°C powder
2 years -80°C in solvent
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.CS(=O)(=O)O

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03176485 Completed Other: Solar Simulator Metastatic Cancer|Melanoma|Colon Cancer|Differentiated Thyroid Cancer|Hepatocellular Carcinoma|Renal Cell Carcinoma|Metastatic Melanoma|HCC|Metastatic Colon Cancer University of Arizona October 17 2014 Not Applicable

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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