NEK7 Inhibitor

Ofirnoflastum (Ofirnoflast) is an orally active first-in-class allosteric NEK7 inhibitor with an IC₅₀ of 46 nM. Ofirnoflastum binds an allosteric site adjacent to NEK7’s ATP-binding pocket, induces conformational shifts, disrupts NEK7-NLRP3 binding, blocks NLRP3 inflammasome assembly, spares NEK7’s physiological functions, and suppresses caspase-1, caspase-8, NF-κB, and TNF activity. Ofirnoflastum reduces pro-inflammatory cytokine production, suppresses ASC specks, IL-1β release, pyroptotic cell death, and leukemic burden, induces apoptosis and erythroid differentiation, restores hematopoiesis, and improves outcomes in colitis models. Ofirnoflastum can be used for the research of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

SLC3037 is a NLRP3 inhibitor which blocks NLRP3 from binding to NEK7 or oligomerization, inhibiting inflammasome caused by MSU and other inflammasome activators. SLC3037 can be used for research of gout, cardiovascular diseases, metabolic syndrome or neurodegenerative diseases.

NLRP3-IN-79 is an orally active NLRP3 inhibitor. NLRP3-IN-79 inhibits NLRP3 inflammasome with an IC₅₀ of 10.69 nM. NLRP3-IN-79 blocks NLRP3 inflammasome assembly by directly binding to NLRP3 and disrupting the NEK7-NLRP3 interaction. NLRP3-IN-79 can be used for the study of NLRP3-driven diseases model, including systemic inflammation, peritonitis, and colitis.

NEK7-IN-2 is a NEK7 inhibitor. NEK7-IN-2 increases the thermal stability of NEK7, disrupts the NEK7-NLRP3 interaction, inhibits NLRP3 inflammasome assembly, and suppresses the release of IL-1β (with an IC₅₀ of 0.048 μM against IL-1β). NEK7-IN-2 can be used for the research of inflammatory diseases.

PPARγ agonist-21 (Compound 9a) is a PPARγ agonist with an EC₅₀ of 3.12 μM. PPARγ agonist-21 activates PPAR-γ to inhibit NF-κB and attenuate NLRP3 inflammasome assembly. PPARγ agonist-21 blocks NLRP3-ASC and NLRP3-NEK7 interaction. PPARγ agonist-21 attenuates the severity of gouty arthritis.