| 產(chǎn)品描述： | Dabrafenib Mesylate (GSK2118436) is the mesylate salt form of dabrafenib, an orally bioavailable inhibitor of B-raf (BRAF) protein with IC50s of 0.7 nM, 5.2 nM and 6.3 nM for B-Raf (V600E), B-Raf (WT) and C-Raf, respectively. |
| 靶點(diǎn)： |
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;Raf |
| 體外研究： |
Dabrafenib displayed compelling inhibitory activity in enzyme and cellular mechanistic assays, and 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). Dabrafenib has a minimal effect in vitro on cells with wild-type B-Raf (HFF IC50 = 3.0 μM) and in tumor cells not harboring the activating B-RafV600E mutation. It is highly selective, exhibiting >500-fold selectivity for B-RafV600E compared to most kinases screened. Significant activity (<100-fold selectivity) was observed for a single kinase in the panel, Alk5. GSK2118436 is significantly less effective at inhibiting SMAD2/3 phosphorylation (IC50 = 3.7 μM) compared with inhibiting ERK phosphorylation (IC50 = 4 nM) in a cellular context. Cellular inhibition of BRAFV600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death |
| 體內(nèi)研究： |
In a BRAFV600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. Dabrafenib is orally bioavailable, doesn’t significantly accumulate after multiple dosing, and causes a reduction of pERK that is sustained for up to 18 h post-dosing after 7 and 14 days of dosing |
| 細(xì)胞實(shí)驗(yàn)： |
Cell lines: A375P cells Concentrations: 8 nM Incubation Time: 1 h Method: A375P cells were transfected with the indicated siRNA for 72 h and treated with 8 nM dabrafenib (+) or DMSO control (?) for 1 h. Lysates were immunoblotted. |
| 動(dòng)物實(shí)驗(yàn)： |
Animal Models: CD1 nu/nu mice bearing A375P F11 (B-RafV600E) tumors Dosages: 0.1, 1, 10, and 100 mg/kg Administration: oral |
| 參考文獻(xiàn)： |
1. Rheault TR, et al. Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors. ACS Med Chem Lett. 2013, 4(3):358-62. 2. Alastair J. King, et al. Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions. PLoS One. 2013, 8(7): e67583. |
| 溶解性： |
soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.624 ml |
8.121 ml |
16.243 ml |
| 5 mM |
0.325 ml |
1.624 ml |
3.249 ml |
| 10 mM |
0.162 ml |
0.812 ml |
1.624 ml |
| 50 mM |
0.032 ml |
0.162 ml |
0.325 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
上海工商
危險(xiǎn)品化學(xué)品經(jīng)營(yíng)許可證（不帶存儲(chǔ)）
營(yíng)業(yè)執(zhí)照(三證合一)
北京