L-779450

基本信息

分子式	C20H14ClN3O
分子量	347.80
存储条件	Freezer -20℃

半岛bd体育手机客户端 描述

L-779450 is a potent and selective B-Raf kinase inhibitor with a Kd of 2.4 nM.

靶点（IC50 & Targe）

Raf

体外研究

L-779450 (L-779,450) shows a high degree of specificity towards Raf. The only other tested kinase inhibited is p38MAPK, which has a kinase domain structurally related to Raf. L-779450 inhibits anchorage-independent growth of human tumor lines at doses ranging from 0.3 to 2?μM[2]. The effects of L-779450 (L-779,450) on TRAIL sensitivity are investigated here in melanoma cell lines with high TRAIL sensitivity (A-375 and SK-Mel-147), moderate sensitivity (Mel-HO, SK-Mel-13, and SK-Mel-28), and permanent resistance (MeWo, Mel-2a, and SK-Mel-103), as well as in TRAIL-selected cell lines with acquired resistance (A-375-TS and Mel-HO-TS). Despite only moderate direct effects of L-779450 on apoptosis, it strongly enhances TRAIL-induced apoptosis in sensitive melanoma cells and overrules TRAIL resistance in Mel-2a, SK-Mel-103, A-375-TS, and Mel-HO-TS. At 24?hours, 16-35% apoptosis induction is obtained[3].

细胞实验

For induction of apoptosis, TRAIL (20?ng/mL), the pan-RAF inhibitor L-779450 (0.1-50?μM), the MEK inhibitor U0126 (20?μM), and the selective BRAF(V600E) inhibitor Vemurafenib/PLX4032 are used. For continuous monitoring cell growth, the xCELLigence system is applied. Relative cell indices correspond to attached cell numbers. Cell cycle analyses are performed for quantification of apoptosis and cell cycle arrest. Cells harvested by trypsinization are stained for 1?hour with propidium iodide (200?mg/mL), and sub-G1 fractions, corresponding to cells with fragmented DNA, are quantified by flow cytometry[3].MCE has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献

[1]. Takle AK, et al. The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4373-6.

[2]. Shelton JG, et al. Differential effects of kinase cascade inhibitors on neoplastic and cytokine-mediated cell proliferation. Leukemia. 2003 Sep;17(9):1765-82.

[3]. Berger A, et al. RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells. J Invest Dermatol. 2014 Feb;134(2):430-440.

安全信息

图形或危害标志
提示语	Danger
危险说明	H301 H315 H319 H335
防范说明	P261 P264 P270 P271 P280 P301+P310+P330 P302+P352 P304+P340+P312 P305+P351+P338 P332+P313 P362 P405
UN号码	2811
危险分类	6.1
包装等级	III