同义名 :	Nec-34
	CAS号 :	375835-43-1
	货号 :	A1497217
	分子式 :	C18H16N4O2S2
	纯度 :	99%+
	分子量 :	384.48
	MDL号 :	MFCD02241236
	存储条件：	Pure form Sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

The receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome[1]. RIPK1 comprises an N-terminal kinase domain, an intermediate domain, and a C-terminal death domain, and the kinase domain is the direct target of Nec-1s[2]. Necrostatin-34 is a RIPK1 kinase inhibitor, stabilizing RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain. Nec-34 showed no significant inhibition against commercially available RIPK2, RIPK3,RIPK4 and RIPK5 at 10 μM, while the RIPK1 kinase activity was effectively blocked by Nec-34 at the same concentration in both biochemical and cellular assays. Nec-34 had no effect on the recruitment and ubiquitination of RIPK1 or the recruitment of TRADD, Sharpin or IKKα/β in complex I, whereas RIPK1 kinase activation, indicated by p-S166 RIPK1, was strongly blocked by Nec-34, as by Nec1s.Necrostatin-34 (10 μM) inhibits the dimerization-induced RIPK1 activation as examined by phosphorylation of Ser166 (p-S166) of RIPK1, a biomarker for RIPK1 activation. Necrostatin-34 may block TNFα-induced complex II formation by inhibiting the activation of RIPK1 kinase. Necrostatin-34 shows IC50 values of 667 nM and 134 nM for TNFα in FADD def-Jurkat cells and L939 cells, respectively. Nec-34 was about 10-fold more potent in inhibiting necroptosis of murine cells than that of human cells[3].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.60mL 0.52mL 0.26mL	13.00mL 2.60mL 1.30mL	26.01mL 5.20mL 2.60mL

参考文献
[1] Theresa Riebeling, Kunzah Jamal,et al. Primidone blocks RIPK1-driven cell death and inflammation. Cell Death Differ. 2021 May;28(5):1610-1626. [2] Degterev, A. et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4, 313–321 (2008). [3]Huyan Meng, et al. Discovery of a cooperative mode of inhibiting RIPK1 kinase. Cell Discov. 2021 Jun 1;7(1):41.