MK-1454 (Merck) is an intratumoral stimulator of interferon (IFN) genes (STING) agonist that is being developed for treatment of advanced solid tumors and lymphomas. The molecule follows Aduro’s ADU-S100 , which was terminated after Ph. II due to a lack of substantial activity. Another chemotype of STING agonist, Eisai’s E7766 , has [...]

This month’s cover molecule, BMS-986278 , is an LPA 1 antagonist and oral (up to 125 mg BID) Ph. II clinical candidate for idiopathic pulmonary fibrosis (IPF) (NCT04308681). Reviewer and nominator Christian Kuttruff says: “While there are two approved molecules for the treatment of IPF (pirfenidone from Roche and nintedanib from BI), there is [...]

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 [...]

The Mirum Pharmaceuticals IBAT bile acid transporter inhibitor, maralixibat , has a long history, having been first patented by scientists at Searle in 1994 and published by the time Searle became part of Pharmacia in 2005 . It was finally approved in Sep. 2021 for treatment of cholestatic pruritis in patients with Alagille Syndrome, and is [...]

Ziretaxestat, an oral autotaxin (ATX) inhibitor originated by Galapagos, once garnered excitement as the first molecule to complete a Ph. III clinical program in idiopathic pulmonary fibrosis since the approvals of nintedanib and pirfenidone. Following the disappointing clinical data and discontinuation of the molecule, this annotation revisits ziritaxestat in the context of other inhibitors, recaps the therapeutic hypothesis and how it was discovered, summarizes notable molecular properties for drug discovery scientists, and discusses what happened and what’s next.