Dabrafenib (GSK2118436)
Dabrafenib (GSK2118436; CAS 1195765-45-7) is a selective inhibitor targeting BRAF kinase mutations at positions V600E, V600K, and V600D. It functions by reversibly binding to the ATP-binding domain of mutant BRAF, suppressing aberrant MAPK pathway activation involved in cellular proliferation and differentiation. Reported inhibitory IC50 values are 0.5 nM (V600E), 0.6 nM (V600K), and 1.9 nM (V600D). Dabrafenib is employed widely in research involving BRAF-mutated metastatic melanoma, demonstrating reduced tumor size and improved patient survival outcomes.
- 1. Xing Tu, Zixing Zou, et al. "Artificial intelligence-enabled discovery of a RIPK3 inhibitor with neuroprotective effects in an acute glaucoma mouse model." Chin Med J (Engl). 2025 Jan 20;138(2):172-184. PMID: 39719694
- 2. Shelby Giza, Jorge A Mojica-Santiago, et al. "Microphysiological system for studying contractile differences in young, active, and old, sedentary adult derived skeletal muscle cells." Aging Cell. 2022 Jul;21(7):e13650. PMID: 35653714
- 3. Yina Liao, Yao Gao, et al. "Melatonin synergizes BRAF-targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling." J Cell Mol Med. 2020 Sep 15. PMID: 32935463
- 4. Cheriyan VT, Alsaab H, et al. "A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers." Oncotarget. 2018 Jul 3;9(51):29680-29697. PMID: 30038713
- 5. Azimi A, Caramuta S, et al. "Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors." Mol Syst Biol. 2018 Mar 5;14(3):e7858. PMID: 29507054
- 6. Sieber J, Wieder N, et al. "GDC-0879, a BRAF(V600E) Inhibitor, Protects Kidney Podocytes from Death." Cell Chem Biol. 2017 Dec 6. PMID: 29249695
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 519.56 |
| Cas No. | 1195765-45-7 |
| Formula | C23H20F3N5O2S2 |
| Solubility | ≥26 mg/mL in DMSO; insoluble in H2O; ≥2.59 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | N-[3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide |
| SDF | Download SDF |
| Canonical SMILES | CC(C)(C)C1=NC(=C(S1)C2=NC(=NC=C2)N)C3=C(C(=CC=C3)NS(=O)(=O)C4=C(C=CC=C4F)F)F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1, 2]: | |
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Cell lines |
B-RafV600E-driven melanoma lines, SKMEL28 and A375P F11, and colorectal carcinoma cells Colo205, HT29 cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μM for 24 h |
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Applications |
Dabrafenib effectively inhibited cell proliferation of B-RafV600E-driven melanoma lines, SKMEL28 and A375P F11 (IC50 = 3 and 8 nM, respectively), and colorectal carcinoma cells Colo205 (IC50 = 7 nM). Moreover, dabrafenib selectively inhibited RIP3 and inhibited RIP3-mediated necroptosis for HT29 cells. |
| Animal experiment [1, 2]: | |
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Animal models |
CD1 nu/nu mice bearing A375P F11 (B-RafV600E) tumors model |
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Dosage form |
0.1, 1, 10, and 100 mg/kg, oral administration, once daily for 14 days or 300 mg/kg, 100 mg/kg dabrafenib (p.o.). |
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Applications |
Dabrafenib dose-dependently inhibited tumor growth and reduced pERK levels in A375P F11 (B-RafV600E) human melanoma tissue in vivo. Additionally, dabrafenib alleviated acetaminophen-induced liver injury in mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Rheault, T. R., Stellwagen, J. C., Adjabeng, G. M., Hornberger, K. R., Petrov, K. G., Waterson, A. G., Dickerson, S. H., Mook, R. A., Jr., Laquerre, S. G., King, A. J., Rossanese, O. W., Arnone, M. R., Smitheman, K. N., Kane-Carson, L. S., Han, C., Moorthy, G. S., Moss, K. G. and Uehling, D. E. (2013) Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors. ACS Med Chem Lett. 4, 358-362 2. Li, J. X., Feng, J. M., Wang, Y., Li, X. H., Chen, X. X., Su, Y., Shen, Y. Y., Chen, Y., Xiong, B., Yang, C. H., Ding, J. and Miao, Z. H. (2014) The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. Cell Death Dis. 5, e1278 |
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| Description | Dabrafenib (GSK2118436) is a inhibitor of mutant BRAFV600 specific with an IC50 value of 0.8 nM. | |||||
| Targets | B-Raf (V600E) | B-Raf | C-Raf | |||
| IC50 | 0.8 nM | 3.2 nM | 5.0 nM | |||
Quality Control & MSDS
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Chemical structure
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