necrosulfonamide

Necrosulfonamide (NSA) is a potent, selective, small-molecule inhibitor of necroptosis that covalently binds and blocks the function of mixed lineage kinase domain-like protein (MLKL), a key executor protein in the necroptotic (regulated necrotic) cell death pathway. NSA acts downstream of receptor-interacting serine-threonine kinase 3 (RIP3) and prevents MLKL-mediated membrane disruption. Notably, NSA is highly species-selective (active on human MLKL but not on murine MLKL due to sequence differences[4][5]). It is widely used in research as a chemical probe of necroptosis, showing efficacy in preclinical models of neurological injury (e.g., spinal cord injury, intracerebral hemorrhage, focal cerebral ischemia, Parkinson's disease), where it exerts neuroprotective, anti-necroptotic, and anti-inflammatory effects[2][3][7][9]. NSA may also impact pyroptosis by interfering with gasdermin D processing at high concentrations, suggesting some off-target effects[4]. NSA is not an approved drug and is used solely for research purposes.

Other names

(2E)-N-[4-[[(3-Methoxy-2-pyrazinyl)amino]sulfonyl]phenyl]-3-(5-nitro-2-thienyl)-2-propenamide