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

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.

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.

Among the small molecule highlights in January’s news were a $100M+ Series A for a PARP1 + PI3Kα-focused company, clinical data with an SLC inhibitor for PKU, a 5-HT2C superagonist for seizures, and a NK1,3 dual antagonist for women’s health. A novel anti-obesity agent from phenotypic screening also made headlines, and the close of a major acquisition may bring relief to the industry. You can read about these notable scientific highlights and more below.

The Drug Hunter team is piloting a new series highlighting notable disclosures in the patent literature to provide our readers a timely and scientifically flavorful synopsis of therapeutic targets being actively pursued, emerging industry breakthroughs, and fascinating chemical matter. Here we highlight 12 patents published in December 2023 that piqued our interest, and compiled a searchable table comprising key information from more than 180 additional patents of potential interest to drug hunters. If you have any suggestions on how to make this more useful, please let us know!

The final set of Molecules of the Month for 2023 is out, and now it’s time to nominate your favorite molecules for 2023’s Molecules of the Year! Nominees should have either been first disclosed in 2023 or had a major new update in 2023 (e.g. clinical trial readout, publication, business transaction, approval). The molecule must have a [...]