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| 25mg |
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Purity: ≥98%
Dabrafenib mesylate (formerly GSK-2118436 mesylate; Tafinlar), the mesylate salt of dabrafenib, is an orally bioavailable BRAF V600 inhibitor that was given FDA approval to treat melanoma in 2013. In cell-free assays, it inhibits BRAF V600 with an IC50 of 0.8 nM.
| Targets |
B-Raf (V600E) (IC50 = 0.7 nM); B-Raf (IC50 = 5.2 nM); C-Raf (IC50 = 6.3 nM)
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|---|---|
| ln Vitro |
Dabrafenib demonstrated strong inhibitory activity in enzyme and cellular mechanistic assays, as well as 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). On cells with wild-type B-Raf and tumor cells lacking the activating B-RafV600E mutation, dabrafenib has little effect in vitro (HFF IC50 = 3.0 μM). Compared to the majority of kinases screened, it is more selective than 500-fold for B-RafV600E. One of the kinases in the panel, Alk5, showed significant activity (<100-fold selectivity), but GSK2118436 is significantly less effective at inhibiting SMAD2/3 phosphorylation (IC50 = 3.7 μM) than it is at inhibiting ERK phosphorylation (IC50 = 4 nM) in a cellular setting[1]. Dabrafenib reduced the activity of the BRAFV600E kinase in cells, which in turn caused a decrease in MEK and ERK phosphorylation, as well as a G1 cell cycle arrest and cell death.
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| ln Vivo |
Dabrafenib, when taken orally, prevented ERK activation, downregulated Ki67, and upregulated p27 in a BRAFV600E-containing xenograft model of human melanoma, which inhibited tumor growth. Dabrafenib is orally bioavailable, does not significantly accumulate after multiple doses, and reduces pERK after 7 and 14 days of dosing[2]. This effect is sustained for up to 18 hours post-dosing.
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| Cell Assay |
For longer-term proliferation assays, cells are plated in 10% FBS-containing RMPI-1640 for 12 days and treated with a single compound or a combination of compounds. The assay involves at least one compound treatment replacement. Using 0.5% methylene blue in 50% ethanol, cells are stained after 12 days. Using a flatbed scanner, pictures are taken.
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| Animal Protocol |
The 26 10-week-old, time-mated, virus-antibody-free SD (Crl:CD[SD]) female rats that were chosen as the test system gave birth to the rat pups. From Day 20 to Day 23 postpartum, mated females are monitored for spontaneous deliveries (the day parturition is complete is designated PND 0). When parturition is complete, on PNDs 3 and 6, litter examinations are carried out. These examinations include external morphologic examinations, gender determination, and individual pup weights. Clinical signs and body weights are used to select parturient dams and their litters for the study, and selected dams and their litters are then randomly assigned to study groups based on clinical observations and PND 3 litter mean body weights. On PND 3 or 4, litters are reduced to four or five males and females, with only a small amount of fostering required to achieve the desired sex ratio. This helps to preserve natural litter sizes as much as possible. Records of the pups raised by the original and foster dams are kept. Paw tattoos are used to identify each puppy. Nonlittermates are placed in subsets to the greatest extent possible. DAB is administered to young male and female rats by oral gavage at a dose volume of 5 ml/kg, based on daily body weight, in a suspension of vehicle, 0.5% hydroxypropylmethylcellulose K15M, and 0.1% (v/v) Tween80 in purified water.
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| References | |
| Additional Infomation |
Dabrafenib mesylate is a methanesulfonate (mesylate) salt prepared from equimolar amounts of dabrafenib and methanesulfonic acid. Used for treatment of metastatic melanoma. It has a role as an antineoplastic agent and a B-Raf inhibitor. It contains a dabrafenib.
Dabrafenib Mesylate is the mesylate salt form of dabrafenib, an orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. See also: Dabrafenib (has active moiety). Drug Indication Treatment of melanoma, Treatment of solid malignant tumours (excluding melanoma) |
| Molecular Formula |
C24H24F3N5O5S3
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|---|---|
| Molecular Weight |
615.66
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| Exact Mass |
615.089
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| Elemental Analysis |
C, 46.82; H, 3.93; F, 9.26; N, 11.38; O, 12.99; S, 15.62
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| CAS # |
1195768-06-9
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| Related CAS # |
Dabrafenib;1195765-45-7
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| PubChem CID |
44516822
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| Appearance |
White to off-white solid powder
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| LogP |
7.033
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
40
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| Complexity |
910
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(C2C([H])=C([H])N=C(N([H])[H])N=2)=C(C2C([H])=C([H])C([H])=C(C=2F)N([H])S(C2C(=C([H])C([H])=C([H])C=2F)F)(=O)=O)N=C1C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H].S(C([H])([H])[H])(=O)(=O)O[H]
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| InChi Key |
YKGMKSIHIVVYKY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H20F3N5O2S2.CH4O3S/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25;1-5(2,3)4/h4-11,31H,1-3H3,(H2,27,28,29);1H3,(H,2,3,4)
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| Chemical Name |
N-[3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide;methanesulfonic acid
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| Synonyms |
GSK2118436A Mesylate; GSK 2118436A Mesylate; GSK-2118436A; GSK2118436B ( Dabrafenib Mesylate); GSK-2118436B Mesylate; GSK 2118436B. Trade name: Tafinlar.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.5 mg/mL (4.06 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (4.06 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 6: 30% PEG400+0.5% Tween80+5% Propylene glycol: 8 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6243 mL | 8.1214 mL | 16.2427 mL | |
| 5 mM | 0.3249 mL | 1.6243 mL | 3.2485 mL | |
| 10 mM | 0.1624 mL | 0.8121 mL | 1.6243 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04439292 | Active Recruiting |
Drug: Dabrafenib Mesylate Drug: Trametinib Dimethyl Sulfoxide |
Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) |
August 12, 2015 | Phase 2 |
| NCT02447939 | Active Recruiting |
Drug: Dabrafenib Drug: Trametinib |
Melanoma | GlaxoSmithKline | May 2017 | Phase 1 |
| NCT01738451 | Active Recruiting |
Drug: GSK2118436 75 mg Drug: Placebo |
Cancer | GlaxoSmithKline | January 22, 2013 | Phase 1 |
| NCT02083354 | Completed | Drug: Dabrafenib Drug: Trametinib |
Cancer Melanoma |
Novartis Pharmaceuticals | March 18, 2014 | Phase 2 |
| NCT01336634 | Completed | Drug: Dabrafenib Drug: Trametinib |
Cancer | Novartis Pharmaceuticals | August 5, 2011 | Phase 2 |
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