molecules of the month

A squaramide-containing, insurmountable CCR6 antagonist for ulcerative colitis. PF-07054894 is a potential first-in-class, oral Ph. I clinical candidate targeting the chemokine receptor CCR6 for ulcerative colitis (NCT05549323). Several companies have pursued antibodies and small molecules targeting CCR6 or its endogenous ligand, CCL20 (e.g. GSK3050002) for immunological conditions including other preclinical squaramides (e.g. Galderma, Allergan, ChemoCentryx) and other series (e.g. Takeda), but PF-07054894 appears to be the first selective CCR6 antagonist to enter clinical development. Structurally, the molecule is notable for its squaramide core, which serves as a urea bioisostere. The molecule emerged from a structure-based drug discovery collaboration between Sosei Heptares and Pfizer, though the squaramide scaffold has further history in CXCR2 modulation (e.g. Schering-Plough CXCR2/CXCR1 antagonist, navarixin/SCH 527123). Pharmacologically,…