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.

Pfizer has announced the FDA-approval of zavegepant ( ZAVZPRET TM , BHV-3500) for the treatment of acute migraine in adults based on positive Ph. II/III results. As the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray [...]

What is it? GB0139 is a selective, inhaled inhibitor of galectin-3 and galectin-1 in Ph. II for IPF and COVID-19 pneumonitis, and is Galecto’s ($GLTO) lead asset. Galecto was founded in 2011 with Lund University academic galectin research leaders Ulf Nilsson and Hakon Leffler, and has had a research focus on galectin-3 modulators to treat [...]

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 [...]

Gamma-secretase is most well-known as a target for Alzheimer’s disease, though such programs have not been successful to date. Nirogacestat is a gamma-secretase inhibitor that Pfizer originally intended to treat AD, but found life at Springworks Therapeutics as a treatment as a first-in-class drug for rare and aggressive desmoid tumors (DTs). Nirogacestat received the first FDA approval for a treatment for desmoid tumors in Nov. 2023, and this article reviews how it was discovered, how the therapeutic hypothesis emerged after confusing assay disconnects, and lessons learned from the program.