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CAS No.: 375835-43-1

Necrostatin-34 Catalog No. CSN33247

Nec-34 can synergize with Nec-1s to inhibit RIPK1 in vitro and in vivo.

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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].
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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.6009 mL
- 13.0047 mL
- 26.0095 mL
- 5 mM
- 0.5202 mL
- 2.6009 mL
- 5.2019 mL
- 10 mM
- 0.2601 mL
- 1.3005 mL
- 2.6009 mL

技术信息

CAS号	375835-43-1	储存条件	粉末 Sealed in dry,2-8°C 液体 -20°C:3-6 月 -80°C:12月
分子式	C18H16N4O2S2	运输	蓝冰
分子量	384.48	别名

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