Necrostatin-1 (Nec-1) serves as a potent inhibitor of necroptosis, capable of crossing the blood-brain barrier, with an effective concentration (EC50) of 490 nM in Jurkat cells. It specifically inhibits RIP1 kinase activity (EC50=182 nM) and also functions as an inhibitor of IDO[1].
体内研究
Additionally, Nec-1 influences tubular dilation and the dynamics of peritubular capillary dilation following RCM exposure. Pre-treatment with a single intraperitoneal dose of Necrostatin-1 (1.65 mg/kg body weight) 15 minutes prior to RCM exposure obstructs the normalization of conditions within the observation timeframe[2].
体外研究
Nec-1 effectively protects L929 cells from TNFα-triggered necrotic death without the need for additional caspase inhibition[1].
Moreover, Nec-1 has been shown to block the expansion of peritubular capillaries induced by radiocontrast media (RCM), highlighting a potentially new function for the RIP1 kinase domain beyond cell death in managing microvascular blood flow and the pathophysiology of contrast-induced acute kidney injury (CIAKI)[2].
At a concentration of 30 μM, Nec-1 increases survival rates in cardiomyocyte progenitor cells (CMPCs) by preventing necrotic cell death[4].
作用机制
Necrostatin 1 is a small molecular that specifically and potently inhibits cell death caused by the stimulation of death-domain receptors in the presence of caspase inhibition. The inhibition of Necrostatin 1 on RIP1 activity was through the T-loop segment.
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