Dabrafenib (GSK2118436A) is a potent ATP-competitive inhibitor of B-Raf, B-Raf V600E and c-Raf with IC50 of 3.2 nM, 0.8 nM and 5.0 nM, respectively. Dabrafenib is selective for Raf kinase, with 400 fold selectivity towards B-Raf over 91% of the other kinases tested. 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. GSK2118436 treatment results in no detectable negative impact on existing systemic immunity or the de novo generation of tumor-specific T cells. Dabrafenib (GSK2118436A) is currently in phase III clinical trial in patients with melanoma.
Int J Mol Sci. 2021 Nov 4;22(21):11951.
BRAF and MEK Inhibitors Affect Dendritic-Cell Maturation and T-Cell Stimulation
Dabrafenib purchased from AbMole
Int J Mol Sci 2018 Jan 18;19(1) pii: E289.
BRAF and MEK Inhibitors Influence the Function of Reprogrammed T Cells: Consequences for Adoptive T-Cell Therapy
Dabrafenib purchased from AbMole
Cell Rep. 2016 Jun 28;16(1):263-77.
BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts.
Dabrafenib purchased from AbMole
Journal of Cell Science. 2016 Jun 1;129(11):2261-72.
PAX5 interacts with RIP2 to promote NF-κB activation and drug-resistance in B-lymphoproliferative disorders.
Dabrafenib purchased from AbMole
EMBO Mol Med. 2015 Jun 23;1104-18.
Intra- and inter-tumor heterogeneity in a vemurafenib-resistant melanoma patient and derived xenografts.
Dabrafenib purchased from AbMole
Cell Rep. 2014 Nov 20;1375-86.
Parallel in vivo and in vitro melanoma RNAi dropout screens reveal synthetic lethality between hypoxia and DNA damage response inhibition.
Dabrafenib purchased from AbMole
Cell Experiment | |
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Cell lines | A375-GFP, 888Mel-MEK1T55delinsRT,SK-MEL-28 |
Preparation method | Dose–response curves were performed as follows: 3,000–6,000 cells were plated per well in a 96-well plate. For each condition, triplicates were plated. The next day, drug was added to the wells. At day 5 of the assay, medium-containing drug was removed and survival was measured by CellTiter-Blue Cell Viability Assay (G8081, Promega). |
Concentrations | 0, 0.25, 0.5, 1, 2.5, 5 µ M |
Incubation time | 5 Days |
Animal Experiment | |
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Animal models | A375 cells infected with pQXCIPGFP, MEK1WT, and MEK1T55delinsRT Mice--Derived Xenografts |
Formulation | Dabrafenib powder was first dissolved in DMSO and consequently, before injection, dissolved in 0.5% hydroxypropylmethylcellulose (Sigma-Aldrich), 0.2% Tween-80 in pH 8.0 distilled H2O. |
Dosages | 30 mg/kg daily (6 days per week) |
Administration | oral gavage |
Molecular Weight | 519.56 |
Formula | C23H20F3N5O2S2 |
CAS Number | 1195765-45-7 |
Solubility (25°C) | DMSO 30 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
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Tinlorafenib
Tinlorafenib (PF-07284890) is an orally active BRAF kinase inhibitor, with IC50 values of 4.25 and 2.7 nM for BRAFV600E/V600K respectively. |
Vemurafenib-d5
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Vemurafenib-d7
Vemurafenib (PLX4032; RG7204; RO5185426) is a first-in-class selective B-RAF inhibitor that inhibits the activity of RAFV600E and c-RAF-1 with IC50 at 31 nM and 48 nM, respectively. Vemurafenib can induce autophagy. |
LUT014
LUT014, a B-Raf inhibitor with an IC50 value of 11.7 nM, was developed for the study of reducing acne-like lesions associated with EGFR inhibitors at restricted doses. |
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