Dabrafenib Mesylate

Catalog No.S5069 Batch:S506905

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Technical Data

Formula

C23H20F3N5O2S2.CH4O3S
Molecular Weight 615.67 CAS No. 1195768-06-9
Solubility (25°C)* In vitro DMSO 100 mg/mL (162.42 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
B-Raf (V600E) [1]
(Cell-free assay)		 B-Raf [1]
(Cell-free assay)		 C-Raf [1]
(Cell-free assay)
0.7 nM 5.2 nM 6.3 nM
In vitro Dabrafenib displayed compelling inhibitory activity in enzyme and cellular mechanistic assays, and in cell proliferation assays in B-RafV600E-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-RafV600E mutation. It is highly selective, exhibiting >500-fold selectivity for B-RafV600E 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 BRAFV600E 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 BRAFV600E-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].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    A375P cells

  • Concentrations

    8 nM

  • Incubation Time

    1 h

  • Method

    A375P cells were transfected with the indicated siRNA for 72 h and treated with 8 nM dabrafenib (+) or DMSO control (−) for 1 h. Lysates were immunoblotted.
Animal Study:

[1]
  • Animal Models

    CD1 nu/nu mice bearing A375P F11 (B-RafV600E) tumors

  • Dosages

    0.1, 1, 10, and 100 mg/kg

  • Administration

    oral

Selleck's Dabrafenib Mesylate has been cited by 72 publications

SB202190 Predicts BRAF-Activating Mutations in Primary Colorectal Cancer Organoids via Erk1-2 Modulation [ Cells, 2023, 12(4)664] PubMed: 36831331
A modified fluctuation-test framework characterizes the population dynamics and mutation rate of colorectal cancer persister cells [ Nat Genet, 2022, 54(7):976-984] PubMed: 35817983
Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma [ Nat Commun, 2022, 13(1):1100] PubMed: 35232962
Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma [ Nat Commun, 2022, 13(1):1381] PubMed: 35296667
Candidate therapeutic agents in a newly established triple wild-type mucosal melanoma cell line [ Cancer Commun (Lond), 2022, 42(7):627-647] PubMed: 35666052
MCU controls melanoma progression through a redox-controlled phenotype switch [ EMBO Rep, 2022, 23(11):e54746] PubMed: 36156348
Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug evaluation [ Front Pharmacol, 2022, 13:1032975] PubMed: 36313330
Effects of dabrafenib and erlotinib combination treatment on anaplastic thyroid carcinoma [ Endocr Relat Cancer, 2022, 29(6):307-319] PubMed: 35343921
SERPINB8 and furin regulate ITGAX expression and affect the proliferation and invasion of melanoma cells [ Exp Dermatol, 2022, 10.1111/exd.14677] PubMed: 36134483
B-Raf inhibitor vemurafenib counteracts sulfur mustard-induced epidermal impairment through MAPK/ERK signaling [ Drug Chem Toxicol, 2022, 1-10] PubMed: 34986718

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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