Dabrafenib free base(GSK2118436A)
Debrafenib free base
CAS: 1195765-45-7
Molecular Formula: C23H20F3N5O2S2
Dabrafenib free base(GSK2118436A) - Names and Identifiers
Dabrafenib free base(GSK2118436A) - Physico-chemical Properties
| Molecular Formula | C23H20F3N5O2S2 |
| Molar Mass | 519.56 |
| Density | 1.443 |
| Melting Point | 214-216oC |
| Boling Point | 653.7±65.0 °C(Predicted) |
| Solubility | Soluble in DMSO (up to 30 mg/ml with warming), or in Ethanol (up to 1 mg/ml with warming). |
| Appearance | White solid. |
| Color | Off-white |
| pKa | 6.62±0.10(Predicted) |
| Storage Condition | -20°C |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. |
| In vitro study | Dabrafenib is selective for Raf kinases and is 400-fold more active against B- Raf than 91% of the other kinases tested. Dabrafenib inhibits B- Raf V600E kinase, resulting in decreased ERK phosphorylation and inhibition of cell proliferation, cell arrest in G1 phase in cancer cells that specifically encode mutated B- Raf V600E. |
| In vivo study | Dabrafenib (oral) inhibits the growth of B- RafV600E mutated melanoma (A375P) and colon cancer (Colo 205) in immunocompromised mice. Dabrafenib (oral) also inhibits tumor growth. |
Dabrafenib free base(GSK2118436A) - Risk and Safety
| HS Code | 29350090 |
Dabrafenib free base(GSK2118436A) - Reference Information
| Melanoma drug | Dapafini (Dabrafenib) is a metastatic melanoma drug developed by GlaxoSmithKline (GSK) in the United States. It is a BRAF inhibitor cancer drug. It is used for medicinal purposes in the form of mesylate. It used to be GSK2118436 and the trade name Tafinlar. on may 29, 2013, the FDA of the us food and drug administration simultaneously approved the listing application of two drug Tafinlar (dapafenib, dabrafenib) and Mekinist (trametinib, trametinib) under GlaxoSmithKline. Tafinlar is approved for the treatment of unresectable melanoma (tumors that cannot be surgically removed) and metastatic melanoma (tumors that have spread to other organs in the body) carrying the BRAF V600E mutation, but not wild-type BRAF melanoma. Mekinist is used to treat unresectable or metastatic melanoma with BRAF V600E or V600K mutation, Mekinist not used to treat melanoma patients who have previously used BRAF inhibitor drugs. The combination of these two drugs is believed to have a more effective and lasting therapeutic effect on melanoma, and the combination of the two drugs is also regarded as the main business opportunity for the two drugs. |
| Synthesis method | The key step in the synthesis of Dapafini (Dabrafenib) is the construction of a 1, 3-thiazole ring, usually with thioamide as 1,3-The dinucleophile and the α-carbonyl halide are directly closed as the 1,2-diphile. Sulfonyl chloride 1 and aniline 2 give sulfonamide 3 under basic conditions. Methylpyrimidine 4 uses the non-nucleophilic strong base LiHMDS to unplug the acidic protons on the methyl group and react with 3 to obtain 5, the latter and NBS undergo α-bromination to obtain 1,2-amphiphilic reagent 6,6 and 1,3-The nucleophilic reagent 7 reacts to close the ring to obtain 8, and then reacts with ammonia to obtain Dapafini (Dabrafenib). fig. 1 is the synthesis roadmap of Dapafini (Dabrafenib). |
| biological activity | Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor, IC50 is 0.8 nM, and its effect on B- Raf(wt) and c-Raf is 4 and 6 times lower. Dabrafenib (GSK2118436, GSK2118436A) is a mutant BRAFV600 specific inhibitor. IC50 is 0.7 nM in cell-free test, and its effect on B- Raf(wt) and c-Raf is 7 and 9 times lower, respectively. |
| Target | Value |
| B-Raf (V600E) (Cell-free assay) | 0.7 nM |
| B-Raf (Cell-free assay) | 5.2 nM |
| C-Raf (Cell-free assay) | 6.3 nM |
Last Update：2024-04-10 22:29:15
