L-779450, 98%, a potent and selective B-Raf kinase inhibitor with a Kd of 2.4 nM
L-779450 , 98% , 一种有效的选择性 B-Raf 抑制剂, Kd 为 2.4 nM
产品编号
920470
CAS
纯度
98%
分子式
C20H14ClN3O
分子量
347.80
品牌
J&K
收藏
5MG
上海: 2
   ¥ 903
10MG
上海: 2
   ¥ 1235

产品描述

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.

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SymbolLSLN
Signal WordDanger
Hazard StatementsH301 H315 H319 H335
Precautionary StatementsP270 P321 P330 P405 P501 P280 P261 P271 P319 P301+P316 P302+P352 P332+P317 P362+P364 P264+P265 P305+P351+P338 P337+P317 P304+P340 P403+P233
UN2811
Hazard Class6.1
Packing GroupIII