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

Customer Product Validation(4)

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 2016-05-29)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
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
NCT02196181 Recruiting BRAF V600E Mutation Present|BRAF V600K Mutation Present|Recurrent Melanoma|Stage IIIA Skin Melanoma|Stage IIIB Skin Melanoma|Stage IIIC Skin Melano  ...more BRAF V600E Mutation Present|BRAF V600K Mutation Present|Recurrent Melanoma|Stage IIIA Skin Melanoma|Stage IIIB Skin Melanoma|Stage IIIC Skin Melanoma|Stage IV Skin Melanoma National Cancer Institute (NCI) April 2016 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

Customer Product Validation (4)


Click to enlarge
Rating
Source J Clin Invest 2014 24(3), 1406-17. Dabrafenib (GSK2118436) purchased from Selleck
Method Western blot
Cell Lines A375P cells
Concentrations 10 uM
Incubation Time 48 h
Results GSK2118436 inhibition produced an additive increase in LC3II/LC3I ratio, but the combination of GSK2118436 with HCQ produced substantial increases in LC3II/LC3I ratio and p62 levels, and the triple drug combination (GSK2118436, GSK1120212, and HCQ) produced the most substantial increase in LC3II/LC3I ratio and buildup of p62, indicative of simultaneous autophagy induction and distal autophagy blockade.

Click to enlarge
Rating
Source J Clin Invest 2014 124(11), 5074-84. Dabrafenib (GSK2118436) purchased from Selleck
Method Western blot
Cell Lines CLL cells
Concentrations 6 uM
Incubation Time 24 h
Results Levels of phosphorylated ERK (pERK) and total ERK (tERK) in enriched CD19+CD5+ CLL cells or CD14+ monocytes were measured by Western blot analysis. CLL cells exposed to dabrafenib or vemurafenib had an elevated pERK/tERK ratio as compared with vehicle(Left). The quantitative results had shown in right(P < 0.01).

Click to enlarge
Rating
Source Transl Res 2014 10.1016/j.trsl.2014.06.005. Dabrafenib (GSK2118436) purchased from Selleck
Method MTT assay
Cell Lines FRO and SW1736 cells
Concentrations 0-5 uM
Incubation Time 72 h
Results Dabrafenib showed inhibition of cell growth with concentrations between 0.5 and 5 uM.

Click to enlarge
Rating
Source Cell Death Dis 2014 5, e1278. Dabrafenib (GSK2118436) purchased from Selleck
Method TUNEL staining
Cell Lines C57Bl/6J mice
Concentrations 100/300 mg/kg
Incubation Time 1 h
Results Dabrafenib protects mice from acetaminophen-induced hepatotoxicity.The pretreatment of mice with dabrafenib (100 mg/kg or 300 mg/kg) apparently eased the acetaminophen-caused liver injury.

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.

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    TAK-632 is a potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf in cell-free assays, respectively, showing less or no inhibition against other tested kinases.

  • GDC-0879

    GDC-0879 is a novel, potent, and selective B-Raf inhibitor with IC50 of 0.13 nM in A375 and Colo205 cells with activity against c-Raf as well; no inhibition known to other protein kinases.

  • GW5074

    GW5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms is noted.

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