AMS-17

AMS-17 is a natural product-inspired, synthetic tertiary sulfonylurea small molecule that acts as a potent and selective inhibitor of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Designed using pharmacophore modeling based on the chalcone isoliquiritigenin, AMS-17 suppresses microglial activation and neuroinflammation by inhibiting the expression of NLRP3 and its downstream signaling components, including ASC, cleaved caspase-1, and inducible nitric oxide synthase (iNOS), thereby reducing the production of proinflammatory cytokines such as IL-1β and TNF-α. In preclinical models, AMS-17 has demonstrated therapeutic potential for vascular dementia (VaD), mild traumatic brain injury (mTBI), cocaine use disorder (CUD), and HIV-associated neurocognitive disorders (HAND) by improving cognitive function, preserving blood-brain barrier integrity, and promoting remyelination.