Dabrafenib (GSK2118436)

For research use only.

Catalog No.S2807 Synonyms: GSK2118436A

196 publications

Dabrafenib (GSK2118436) Chemical Structure

CAS No. 1195765-45-7

Dabrafenib (GSK2118436, GSK2118436A) is a mutant BRAFV600 specific inhibitor with IC50 of 0.7 nM in cell-free assays, with 7- and 9-fold less potency against B-Raf(wt) and c-Raf, respectively.

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Selleck's Dabrafenib (GSK2118436) has been cited by 196 publications

Purity & Quality Control

Choose Selective Raf Inhibitors

Biological Activity

Description Dabrafenib (GSK2118436, GSK2118436A) is a mutant BRAFV600 specific inhibitor with IC50 of 0.7 nM in cell-free assays, with 7- and 9-fold less potency against B-Raf(wt) and c-Raf, respectively.
Targets
B-Raf (V600E) [3]
(Cell-free assay)
B-Raf [3]
(Cell-free assay)
C-Raf [3]
(Cell-free assay)
0.7 nM 5.2 nM 6.3 nM
In vitro

Dabrafenib is selective for Raf kinase, with 400 fold selectivity towards B-Raf over 91% of the other kinases tested. Dabrafenib inhibits B-RafV600E kinase, leading to decreased ERK phosphorylation and inhibition of cell proliferationby an initial arrest in the G1 phase of the cell cycle in cancer cells that specifically encode the mutation for B-RafV600E. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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SK-MEL-28 NIjyRWZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= Ml[yOFghcA>? NVToVYhQT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hW0tvTVXMMVI5KGOnbHzzJIhiemKxcnnu[{BDWkGIIG[2NFBGKG23dHHueEBxemWrbnP1ZoF1\WRiZn;yJFEhcHJiZn;scI94\WRiYomgbZJz[WSrYYTpc44hd2ZiMT6xN{BsXy:vMjDVWk1tcWeqdDDmc5IhPSCvaX7zJI1m[XO3cnXkJIFnfGW{IES4JIhzeyC{ZYPhfpVzcW5iYYPzZZk> NW\Ib3RyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke3O|QyOzdpPkK3O|c1OTN5PD;hQi=>
SK-MEL-28 MnjGR5l1d3SxeHnjbZR6KGG|c3H5 NV\Y[GhIPDhiaB?= MVPDfZRwe3SjdHnjJIFkfGm4aYT5JIlvKGi3bXHuJHNMNU2HTD2yPEBk\WyuczDoZZJjd3KrbnegRnJCTiCYNkCwSUBufXSjboSgZZQhOSCjbnSgN|AhfU1ibXXhd5Vz\WRiYX\0[ZIhPDhiaILzJJJme2G8dYLpckBie3OjeR?= NGXXWFQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{e3OFE{Pyd-Mke3O|QyOzd:L3G+
DAOY NVzURpYxWHKrbXHyfUB{[3KnZX6gZZN{[Xl? NVrBfYY4eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFTBU3kh[2WubIO= NVTEbpk{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643 MX;Qdolu[XK7IIPjdoVmdiCjc4PhfS=> NWHM[HlHeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=> NV7KSmpoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC NY\jNlFVWHKrbXHyfUB{[3KnZX6gZZN{[Xl? NF7KeG9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=> Mlr1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pMEK / pERK / ERK; 

PubMed: 31158244     


Cell lines as shown were treated with dabrafenib, over a dose range, for 1 hour. UT = untransfected.  Expression and/or phosphorylation of the indicated proteins were assessed by immunoblot.

p-S6 / p-AKT308 / p-AKT473; 

PubMed: 24735930     


Western blot analysis of phosphorylated proteins in MAPK and the PI3K-AKT pathway after 24 hours exposure to increasing concentrations of dabrafenib.

β-catenin; 

PubMed: 29167314     


HT-29 cells were treated with BRAF inhibitors Dabrafenib (2 μM), GDC-0879 (4 μM) or Vemurafenib (2 μM) for indicated times. The whole cell lysates were used for western blot with indicated antibodies.

31158244 24735930 29167314
Growth inhibition assay
IC50; 

PubMed: 24735930     


A panel of 23 BRAF(V600) mutant human melanoma cell lines was treated with serial dilutions (1-10,000 nM) of dabrafenib (A) for 72-120 hours to assess cell viability. The bars represent the average IC50 value of two or more independent experiments in duplicates and the error bars represent the SEM. 

24735930
In vivo Dabrafenib (orally administrated) inhibits the growth of B-RafV600E mutant melanoma (A375P) and colon cancer (Colo205) human tumor xenografts, growing subcutaneously in immuno-compromised mice. [1]

Protocol

Solubility (25°C)

In vitro DMSO 30 mg/mL (57.74 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+45% PEG 300+2% Tween 80+ddH2O
For best results, use promptly after mixing.
5 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 519.56
Formula

C23H20F3N5O2S2

CAS No. 1195765-45-7
Storage powder
in solvent
Synonyms GSK2118436A
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

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 ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04547946 Not yet recruiting Drug: dabrafenib + trametinib Malignant Melanoma Novartis Pharmaceuticals|Novartis April 30 2021 --
NCT04775095 Recruiting -- Non Small Cell Lung Cancer|BRAF V600 Mutation Intergroupe Francophone de Cancerologie Thoracique|Novartis March 8 2021 --
NCT04666272 Recruiting Drug: dabrafenib|Drug: trametinib Melanoma Novartis Pharmaceuticals|Novartis December 31 2020 --
NCT04452877 Active not recruiting Drug: Dabrafenib|Drug: Trametinib Carcinoma Non-Small-Cell Lung Novartis Pharmaceuticals|Novartis August 19 2020 Phase 2

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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

Raf Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID