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Necrostatin-34

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Chemical Structure| 375835-43-1 同义名 : Nec-34
CAS号 : 375835-43-1
货号 : A1497217
分子式 : C18H16N4O2S2
纯度 : 99%+
分子量 : 384.475
MDL号 : MFCD02241236
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(312.11 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
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.