BAL-0598 is a potent and selective, non-covalent inhibitor of human NLRP3, binds NLRP3 NACHT with a steady-state KD of 193 nM in SPR assays.
BAL-0598 inhibits LPS and nigericin-induced NLRP3 signaling in a range of human cell types, including THP-1, monocytes, iMacs, and HMDM.
BAL-0598 also inhibits NLRP3 activation by stimuli such as MSU and prevents NLRP3-dependent ASC speck formation.
BAL-0598 does not inhibit NLRP3 activation in mouse macrophages.
BAL-0598 inhibit NLRP3 activation in mouse macrophages expressing human NLRP3 in a nanomolar range.
BAL-0598 has IC50 of 63.9 nM in IL-1β release assay from PMA-differentiated THP-1 cells.
BAL-0598 reduces the IL-1β response in mice model of peritonitis with ED50 of 28.6 mg/kg.
BAL-0598 inhibits disease-associated NLRP3 mutations, potently inhibits A352V, K565E, E567G, K568N, and G569R at levels similar to WT NLRP3.
1. Wilhelmsen K, et al. Discovery of potent and selective inhibitors of human NLRP3 with a novel mechanism of action. J Exp Med. 2025 Nov 3;222(11):e20242403.
