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Reagents and instruments for immunology, cell biology and molecular biology.

Dabrafenib [1195765-45-7]

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Cat# HY-14660-10mg

Size : 10mg

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Phone : +1 850 650 7790

Brand : MedChemExpress

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Description

Dabrafenib (GSK2118436A) is an ATP-competitive inhibitor of Raf with IC₅₀s of 5 nM and 0.6 nM for C-Raf and B-Raf^V600E, respectively^[4].

IC₅₀ & Target^[4]

BRaf^V600E

0.6 nM (IC₅₀)

CRAF

5 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	0.011 μM Compound: 2	Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay	[PMID: 25965804]
A-375	IC₅₀	0.457 nM Compound: DB	Antiproliferative activity against human A-375 cells assessed as inhibition of cell growth measured after 5 days by MTT assay Antiproliferative activity against human A-375 cells assessed as inhibition of cell growth measured after 5 days by MTT assay	[PMID: 34958586]
A-375	IC₅₀	1 nM Compound: 3	Inhibition of B-Raf V600E mutant in human A375 cells assessed as ERK phosphorylation preincubated for 1 hr by Western blot method Inhibition of B-Raf V600E mutant in human A375 cells assessed as ERK phosphorylation preincubated for 1 hr by Western blot method	[PMID: 27085672]
A-375	IC₅₀	150 nM Compound: 2	Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	26 nM Compound: 2	Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
A-375	IC₅₀	6 nM Compound: 2	Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue	[PMID: 25965804]
HCT-116	IC₅₀	5.88 μM Compound: 2	Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA	[PMID: 25965804]
HepG2	IC₅₀	3.7 μM Compound: 12, GSK2118436, Dabrafenib	Inhibition of Alk5 in TGF-beta-stimulated human HepG2 cells assessed as decrease in Smad2 phosphorylation treated for 45 mins prior to TGF-beta stimulation measured after 60 mins by odyssey blot scanner analysis Inhibition of Alk5 in TGF-beta-stimulated human HepG2 cells assessed as decrease in Smad2 phosphorylation treated for 45 mins prior to TGF-beta stimulation measured after 60 mins by odyssey blot scanner analysis	[PMID: 24900673]
MIA PaCa-2	EC₅₀	529 nM Compound: 3	Inhibition of wild type B-Raf in human MIAPaCa2 cells assessed as reduction in ERK phosphorylation preincubated for 1 hr by Western blot method Inhibition of wild type B-Raf in human MIAPaCa2 cells assessed as reduction in ERK phosphorylation preincubated for 1 hr by Western blot method	[PMID: 27085672]
Sf9	IC₅₀	250 nM Compound: 58	Inhibition of human full length N-terminal GST-tagged RIPK3 expressed in baculovirus infected sf9 insect cells assessed as reduction in MBP phosphorylation using MBP as substrate by kinase-Glo luminescence assay Inhibition of human full length N-terminal GST-tagged RIPK3 expressed in baculovirus infected sf9 insect cells assessed as reduction in MBP phosphorylation using MBP as substrate by kinase-Glo luminescence assay	[PMID: 31622096]
Sf9	IC₅₀	9 nM Compound: 1	Inhibition of recombinant human N-terminal GST-6His tagged BRAF V600E mutant (417 to 766 residues) expressed in baculovirus infected Sf9 cells preincubated with substrate followed by protein and ATP addition measured after 60 mins by scintillation counter Inhibition of recombinant human N-terminal GST-6His tagged BRAF V600E mutant (417 to 766 residues) expressed in baculovirus infected Sf9 cells preincubated with substrate followed by protein and ATP addition measured after 60 mins by scintillation counter	[PMID: 27774137]
SK-MEL-28	IC₅₀	3 nM Compound: 12, GSK2118436, Dabrafenib	Inhibition of B-Raf V600E mutant-driven SK-MEL-28 cell proliferation after 72 hrs by CellTiter-Glo luminescent assay Inhibition of B-Raf V600E mutant-driven SK-MEL-28 cell proliferation after 72 hrs by CellTiter-Glo luminescent assay	[PMID: 24900673]
SK-MEL-28	IC₅₀	4 nM Compound: 12, GSK2118436, Dabrafenib	Inhibition of B-Raf V600E mutant in human SK-MEL-28 cells assessed as decrease in ERK phosphorylation incubated for 1 hr by immunoassay Inhibition of B-Raf V600E mutant in human SK-MEL-28 cells assessed as decrease in ERK phosphorylation incubated for 1 hr by immunoassay	[PMID: 24900673]
SK-MEL-28	IC₅₀	43 nM Compound: 6	Cytotoxicity against human SK-MEL-28 cells after 72 hrs by CellTiter-Glo assay Cytotoxicity against human SK-MEL-28 cells after 72 hrs by CellTiter-Glo assay	[PMID: 29461827]

In Vitro

Dabrafenib (GSK2118436, 1 μM) with 0.01 μM GSK1120212 inhibits more than 90% of cell growth in the NRAS mutant clones. GSK2118436 is sufficient to reduce S6P phosphorylation in A375^[1]. Dabrafenib suppresses the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6^[2]. Dabrafenib inhibits the release of HMGB1 and downregulates HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Dabrafenib-treated females have mostly immature reproductive tracts with no evidence of ovulation, similar to age-matched controls; however, DAB-treated females have keratinized and histologically open vaginas^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

519.56

Formula

C₂₃H₂₀F₃N₅O₂S₂

CAS No.

1195765-45-7

Appearance

Solid

Color

White to off-white

SMILES

CC(C)(C)C1=NC(C2=C(F)C(NS(C3=C(F)C=CC=C3F)(=O)=O)=CC=C2)=C(C4=CC=NC(N)=N4)S1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : ≥ 33 mg/mL (63.52 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.9247 mL	9.6235 mL	19.2471 mL
5 mM	0.3849 mL	1.9247 mL	3.8494 mL
10 mM	0.1925 mL	0.9624 mL	1.9247 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 4

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: 2.5 mg/mL (4.81 mM); Suspended solution; Need ultrasonic
Protocol 5

Add each solvent one by one: 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.81 mM); Clear solution

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 30% PEG400 0.5% Tween-80 5% Propanediol 64.5% H2O
Solubility: 5 mg/mL (9.62 mM); Suspended solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 0.5% HPMC in Water
Solubility: 2.5 mg/mL (4.81 mM); Suspended solution; Need ultrasonic

Purity & Documentation

Purity: 99.94%

Data Sheet (286 KB) SDS (480 KB)

COA (259 KB) HNMR (268 KB) RP-HPLC (244 KB) LCMS (105 KB) Elemental Analysis Report (117 KB)

Handling Instructions (2659 KB)

References

[1]. Greger JG, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther, 2012, 11(4), 909-920. [Content Brief]

[2]. Lee S, et al. Anti-inflammatory effects of dabrafenib on polyphosphate-mediated vascular disruption. Chem Biol Interact. 2016 Jul 22. [Content Brief]

[3]. Jung B, et al. Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses. BMB Rep. 2016 Apr;49(4):214-9. [Content Brief]

[4]. Alexander M Menzies, et al. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012; 6: 391–405. [Content Brief]

[5]. Posobiec LM, et al. Early Vaginal Opening in Juvenile Female Rats Given BRAF-Inhibitor Dabrafenib Is Not Associated with Early Physiologic Sexual Maturation. Birth Defects Res B Dev Reprod Toxicol. 2015 Dec;104(6):244-52. [Content Brief]

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Dabrafenib [1195765-45-7]

Cat# HY-14660-10mg

Contact local distributor :

Brand : MedChemExpress

Contact local distributor :

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