GLPG1690: The First Clinical Autotaxin (ATX) Inhibitor for IPF
ziritaxestat
oral ATX inhibitor negative outcomes in Ph. III in IPF (200-600 mg QD) from HTS and optimization JAMA, May 9, 2023 Galapagos SASU, Romainville, FR
Other molecules you may be interested in
X-165
X-165 is an autotaxin inhibitor clinical candidate for idiopathic pulmonary fibrosis discovered using a 3-cycle DEL screen of 225M compounds derived from amide couplings. An unusual spirocyclic amine building block was responsible for most of their non-phosphonate-containing high-enrichment hits. The initially resynthesized hits had [...]
nirogacestat
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.
zavegepant
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 [...]
resmetirom
On Mar. 14th, 2024, resmetirom (REZDIFFRA™) became the first and only medicine approved by the FDA for the treatment of NASH (non-alcoholic steatohepatitis, aka MASH). Resmetirom, an oral, liver-targeting, once-daily THR-β-selective agonist originally discovered at Roche Nutley, was first highlighted as a Molecule of the Month in Dec. 2022. Now, with the FDA’s accelerated approval, this 2023 Molecule of the Year nominee reflects a historic milestone for liver drug discovery. This article reviews how the molecule works, how it was discovered, and why it’s a big deal.
“compound 54c”
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 [...]