Dabrafenib (GSK2118436)

Catalog No.S2807
5 5 6 Product Citations

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

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In DMSO USD 180 In stock
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Dabrafenib (GSK2118436) Chemical Structure

Dabrafenib (GSK2118436) Chemical Structure
Molecular Weight: 519.56

Validation & Quality Control

Customer Reviews(4)

Quality Control & MSDS

Related Compound Libraries

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

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

  • Most Potent Raf Inhibitor

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  • FDA-approved Inhibitor

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  • Newest Raf Inhibitor

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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, with 4- and 6-fold less potency against B-Raf(wt) and c-Raf, respectively.
Targets B-Raf (V600E) [1] B-Raf [1] C-Raf [1]
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]
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

Protocol(Only for Reference)

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

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
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 2014-12-20)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02082665 Not yet recruiting Cancer GlaxoSmithKline December 2014 Phase 1
NCT02200562 Recruiting Stage III or IV Melanoma University of Utah December 2014 Phase 1|Phase 2
NCT02082665 Not yet recruiting Cancer GlaxoSmithKline December 2014 Phase 1
NCT02200562 Recruiting Stage III or IV Melanoma University of Utah December 2014 Phase 1|Phase 2
NCT02124772 Not yet recruiting Cancer GlaxoSmithKline November 2014 Phase 1

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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 (DMSO, water, etc.)
Synonyms
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

Research Area

Customer Reviews (4)


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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).

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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.

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.

Product Citations (6)

Tech Support & FAQs

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