molecules of the month

A p38α-MK2 kinase complex inhibitor for inflammation. Zunsemetinib (ATI-450, CDD-450) is a p38α-MK2 complex inhibitor discovered by Confluence Technologies and developed by Confluence spinout, Aclaris Therapeutics. The molecule binds to a site formed from the modified p38MAPK ATP binding pocket and MK2 when the two proteins interact, inhibiting the heterodimeric complex. The complex inhibitor represents one of the more promising attempts to drug p38α, a kinase which has been long pursued in a range of indications but challenging to target due to systemic toxicities (hepatotoxicity, CNS- and cardiac toxicities), and tachyphylaxis (loss of efficacy over time). Unfortunately, the molecule recently failed to meet endpoints in a Ph. IIa trial for hidradentis suppurativa (NCT05216224), an immune-mediated skin disorder, though the company…