necrostatin-1S

Necrostatin-1S (Nec-1s) is a potent, highly selective, and metabolically stable small-molecule allosteric inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Developed as an optimized analog of necrostatin-1 (Nec-1), Nec-1s lacks the off-target inhibitory activity against indoleamine 2,3-dioxygenase (IDO) that is characteristic of its predecessor, while exhibiting approximately two-fold greater potency in blocking RIPK1-mediated necroptosis. It binds to the allosteric pocket of the RIPK1 kinase domain, preventing its autophosphorylation and subsequent activation of the RIPK3-MLKL signaling cascade. Nec-1s is widely utilized as a chemical probe in preclinical research to investigate the role of necroptosis and RIPK1-dependent inflammation in various pathological conditions, including neurodegenerative diseases (such as Alzheimer's disease and amyotrophic lateral sclerosis), ischemia-reperfusion injury, and acute inflammatory disorders.

Other names

7-Cl-O-Nec-17-Cl-O-necrostatin-1Nec-1SNec1SNec 1SNecrostatin-2 racemateNecrostatin2 racemateNecrostatin 2 racemateRIP1 Inhibitor IIRIP-1 Inhibitor IIRIP 1 Inhibitor IInecrostatin-1snecrostatin1snecrostatin 1s