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Dabrafenib Mesylate Raf inhibitor

Name: Dabrafenib Mesylate
Brand: Selleck Chemicals
SKU: S5069
Availability: InStock
Rating: 5 (72 reviews)

Cat.No.S5069

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.

Chemical Structure

Molecular Weight: 615.67

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	Ras ERK p38 MAPK JNK MEK S6 Kinase MAP4K TAK1 Mixed Lineage Kinase ASK MNK MAPKAPK2 KLF TOPK
Related Products	PLX-4720 LY3009120 AZ 628 GDC-0879 SB590885 TAK-632 RAF265 (CHIR-265) GW5074 Avutometinib (Ro 5126766) PLX7904 Plixorafenib (PLX8394) ZM 336372 Naporafenib (LXH254) Lifirafenib (BGB-283) Agerafenib (CEP-32496) Tovorafenib (MLN2480) Belvarafenib B-Raf inhibitor 1 (Compound 13) dihydrochloride RAF709 CCT196969 RKIP Antibody [E4D22] HG6-64-1 Tinlorafenib TBAP-001 Flezurafenib GNE-9815 Phospho-c-Raf (Ser338) Antibody [F15C8] B-Raf IN 1 Raf inhibitor 1 c-Raf Antibody [E17B21]

Chemical Information, Storage & Stability

Molecular Weight	615.67	Formula	C₂₃H₂₀F₃N₅O₂S₂.CH₄O₃S	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1195768-06-9	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	GSK2118436 Mesylate			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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (162.42 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (8.12mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.416mg/ml (0.68mM)	Taking the 1 mL working solution as an example, add 50 μL of 8.32 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

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

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	B-Raf (V600E) ^[1] (Cell-free assay) 0.7 nM B-Raf ^[1] (Cell-free assay) 5.2 nM C-Raf ^[1] (Cell-free assay) 6.3 nM
In vitro	Dabrafenib displayed compelling inhibitory activity in enzyme and cellular mechanistic assays, and in cell proliferation assays in B-Raf^V600E-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-Raf^V600E mutation. It is highly selective, exhibiting >500-fold selectivity for B-Raf^V600E 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 BRAF^V600E 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].
In vivo	In a BRAF^V600E-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].
References	[1] https://pubmed.ncbi.nlm.nih.gov/24900673/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701070/

Applications

Methods	Biomarkers	Images	PMID
Western blot	pMEK / pERK / ERK p-S6 / p-AKT308 / p-AKT473 β-catenin		31158244
Growth inhibition assay	IC50		24735930

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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