Dabrafenib (GSK2118436)

Catalog No.S2807

Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor with IC50 of 0.8 nM in cell-free assays, with 4- and 6-fold less potency against B-Raf(wt) and c-Raf, respectively.

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Dabrafenib (GSK2118436) Chemical Structure

Dabrafenib (GSK2118436) Chemical Structure
Molecular Weight: 519.56

Validation & Quality Control

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Quality Control & MSDS

Related Compound Libraries

Dabrafenib (GSK2118436) is available in the following compound libraries:

Raf Inhibitors with Unique Features

  • Pan Raf Inhibitor

    AZ 628 Pan-Raf inhibitor, BRAF, IC50=105 nM; BRAFV600E, IC50=34 nM; c-Raf-1, IC50=29 nM.

  • Most Potent Raf Inhibitor

    PF-04880594 C-Raf, IC50=0.39 nM; B-Raf, IC50=0.19 nM.

  • FDA-approved Raf Inhibitor

    Sorafenib Tosylate Approved by FDA for advanced renal cancer。

  • Newest Raf Inhibitor

    TAK-632 Potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf, respectively, showing less or no inhibition against other tested kinases.

Product Information

  • Compare Raf Inhibitors
    Compare Raf Products
  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor with IC50 of 0.8 nM in cell-free assays, with 4- and 6-fold less potency against 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)
IC50 0.8 nM 3.2 nM 5.0 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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... Click to View More Cell Line Experimental Data

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]
Features

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Sylvie Laquerre, et al. 2009, EORTC International Conference. Abst B88.

[2] Greger JG, et al. Mol Cancer Ther, 2012, 11(4), 909-920.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02447939 Not yet recruiting Melanoma GlaxoSmithKline September 2016 Phase 1
NCT02672358 Not yet recruiting Non-Small-Cell Lung Cancer Novartis Pharmaceuticals|Novartis July 2016 Phase 2
NCT02684058 Not yet recruiting Anaplastic Astrocytoma|Glioblastoma|Giant Cell Glioblastoma|Gliosarcoma|Anaplastic Oligodendroglioma|Anaplastic Oligoastrocytoma|Anaplastic Ependym  ...more Anaplastic Astrocytoma|Glioblastoma|Giant Cell Glioblastoma|Gliosarcoma|Anaplastic Oligodendroglioma|Anaplastic Oligoastrocytoma|Anaplastic Ependymoma|Choroid Plexus Carcinoma|Anaplastic Ganglioglioma|Pineal Parenchymal Tumor|Pineoblastoma|Medulloblastoma|PNET|Rhabdoid Tumor|Perineurioma|MPNST|Malignant Meningloma|Anaplastic Hemangiopericytoma Novartis Pharmaceuticals|Novartis May 2016 Phase 2
NCT02700763 Not yet recruiting Melanoma University Medical Center Groningen April 2016 Phase 1
NCT02382549 Recruiting Melanoma Craig L Slingluff, Jr|National Cancer Institute (NCI)|Uni  ...more Craig L Slingluff, Jr|National Cancer Institute (NCI)|University of Virginia April 2016 Phase 1|Phase 2

view more

Chemical Information

Download Dabrafenib (GSK2118436) SDF
Molecular Weight (MW) 519.56
Formula

C23H20F3N5O2S2

CAS No. 1195765-45-7
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 30 mg/mL (57.74 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 8 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name N-(3-(5-(2-aminopyrimidin-4-yl)-2-tert-butylthiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

Tech Support

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