Chemoproteomics finds a brain-penetrant covalent NLRP3 inhibitor at a new allosteric site
- Chemoproteomic profiling was used to find a covalent NLRP3 inhibitor.
- The compound is brain-penetrant and is described as binding a previously unreported allosteric pocket.
- Only the title and issue details were accessible when this was written, so potency, selectivity and efficacy data are not covered.
💡 Points
NLRP3 has plenty of reversible MCC950-type chemistry, so the interest here is a different pocket and a route in neuroinflammation via brain exposure. Covalent warheads in a CNS drug still need clean proteome-wide selectivity, and the residue targeted matters for resistance and species translation. A new pocket gives other groups a second place to design against.