Drug-Induced Liver Injury: A Medicinal Chemist’s Perspective

The highly anticipated First Time Disclosures session at the ACS Spring 2024 Meeting in New Orleans, organized by Nicole Goodwin and H. Rachel Lagiakos, presented a variety of new orally available small molecules. In case you missed any of these exciting molecules, from Oric’s CD73 inhibitor to Deciphera’s first-in-class ULK1/2 inhibitor, this article provides the structures and targets for the novel molecules disclosed at the session.

Drug Hunter has sifted through news articles, press releases, financial disclosures, SEC filings, and more to bring you a roundup of 2023’s biggest mergers and acquisitions (M&A) in the drug discovery world. Following our open-access industry overview, in the final installment of this four-part series we bring you the biologics-focused deals opening checkbooks in 2023.

PRMT5 is an epigenetic “synthetic lethality” target that has attracted much attention among drug hunters. The first generation of PRMT5 inhibitors was limited by systemic toxicities resulting in a cooling of industry interest, until the recent identification of tumor-specific inhibitors. These second-generation compounds target the MTA:PRMT5 complex in MTAP-deleted cancers—15% of all tumors—leading to a revival of the target. Read on to find out which companies are prevailing in the search for a first-in-class PRMT5 inhibitor and how their clinical compounds differentiate.

The discovery that individuals with null mutations in the NaV1.7 exhibited pain insensitivity sparked interest in targeting NaV1.7 to potentially treat pain. Despite the potential of selectively inhibiting sodium channels like NaV1.7, NaV1.8, and NaV1.9 for pain management, developing selective inhibitors suitable for clinical use has proven challenging. This article complements our coverage of VX-548, NaV1.8 as a critical target in pain management, and our NaV1.8 compound roundup and provides a reminder of noteworthy preclinical and clinical NaV1.7 small molecule inhibitors as of April 2024.

Peptidic GLP-1R agonists have received significant media coverage over the past year for their astounding efficacy in several indications. While most of the recent fanfare has been related to their role in weight loss, GLP-1R agonists have been a mainstay of the type 2 diabetes treatment landscape for the past 2 decades. GLP-1R agonists have also recently shown efficacy in reducing heart disease risk and treating certain chronic kidney diseases. Here’s a recap of the March 14th, 2024, Flash Talk, from Oliver Philps.