Home MAPK Raf inhibitor Dabrafenib Mesylate For research use only.

Dabrafenib Mesylate

Synonyms: GSK2118436 Mesylate

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

Dabrafenib Mesylate Chemical Structure

CAS No. 1195768-06-9

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Dabrafenib Mesylate Related Products

Signaling Pathway

Raf Signaling Pathways

Raf Signaling Pathway

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
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].
Cell Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pMEK / pERK / ERK p-S6 / p-AKT308 / p-AKT473 β-catenin 31158244
Growth inhibition assay IC50 24735930
In Vivo
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].
Animal Research Animal Models CD1 nu/nu mice bearing A375P F11 (B-RafV600E) tumors
Dosages 0.1, 1, 10, and 100 mg/kg
Administration oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03176485 Completed
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

Chemical Information & Solubility

Molecular Weight 615.67 Formula

C23H20F3N5O2S2.CH4O3S
CAS No. 1195768-06-9 SDF --
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
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (162.42 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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