NA-184

NA-184 is an experimental, brain-penetrant small-molecule calpain-2 inhibitor optimized from earlier peptidyl α‑ketoamide scaffolds to achieve high selectivity for calpain-2 over calpain-1, with nanomolar potency against human calpain-2 and no detectable inhibition of calpain-1 up to micromolar concentrations.[1][3][5] The compound, chemically described as (S)-2-(3-benzylureido)-N-((R,S)-1-((3-chloro-2-methoxybenzyl)amino)-1,2-dioxopentan-3-yl)-4-methylpentanamide, shows favorable pharmacokinetics including plasma and liver stability and blood–brain barrier permeability.[3][5] In rodent controlled cortical impact models of traumatic brain injury, systemic administration of NA-184 after injury selectively suppresses calpain-2 activation in brain tissue, significantly reduces cortical cell death, and provides robust neuroprotection in both mice and rats of both sexes, leading to its selection for further preclinical development and planned clinical trials as a disease-modifying therapy for traumatic brain injury and potentially other acute neurodegenerative conditions.[1][2][3][5][7]

Other names

NA-184NA184NA 184(S)-2-(3-benzylureido)-N-((R,S)-1-((3-chloro-2-methoxybenzyl)amino)-1,2-dioxopentan-3-yl)-4-methylpentanamide