molecules of the month

Context. Compound 14f (Kyowa Kirin) is an oral ChemR23 inhibitor with two acidic sites. Nominated by Bryan McKibben, this article describes a scaffold hopping exercise to address the short half-life of previously described chemical matter, and the successful development of in-vivo tool inhibitors to probe ChemR23 biology in animal models of inflammatory disease. An earlier ChemR23 inhibitor from Kyowa was previously highlighted in Jul. 2020. This article also describes the design of a fluorescein-labeled probe for the target. Target. ChemR23 (CMKLR1) is a chemokine-like, GPCR receptor implicated in dendritic, macrophage and NK-cell related inflammatory diseases including systemic lupus erythematosus (SLE), psoriasis and atherosclerosis. The ChemR23 inhibitor was developed with the intention of suppressing the migration of plasmacytoid dendritic cells (pDCs),…