molecules of the month

JAK kinases are now well-established targets in immunology, but the class has always had safety concerns hanging over it. The safety issues were exacerbated by a recent FDA decision to expand the black box warnings for the class for major cardiovascular events. Inhaled, lung-restricted JAK inhibitors have been of interest because they could leverage the established efficacy of the class while avoiding toxicities due to systemic exposure. Reviewer Naomi Rajapaksa says, “The GSK paper highlights both an underappreciated role aldehyde oxidase (AO) can play in the lung as well as a challenge of achieving low lung clearance with high systemic clearance.” The authors unexpectedly encountered significant aldehyde oxidase metabolism in the lung, and demonstrated that is likely a relevant phenomenon…