MYT1, Pan-RAF, Pan-RAS and More: Dec. ’23 Compound Collection

In June, we saw several FDA approvals for treatments targeting primary biliary cholangitis and COPD. The industry witnessed multibillion- and multimillion-dollar deals across various therapeutic areas. Advances were made in obesity therapeutics, with novel targets and clinical readouts for GLP-1 agonists and NLRP3 inhibitors. Alkermes and Takeda reported results for OX2R agonists in narcolepsy, while an antimalarial drug showed promise in PCOS. Despite these advancements, there were clinical trial failures for key molecules. Here's a recap of the most notable news highlights from June 2024!

DILI is a leading cause of acute liver failure, accounting for half of these cases and often resulting in drug withdrawals. Understanding and managing DILI risk as a medicinal chemist involves exploring the intricate interplay among properties and structural features. In this article, we provide a medicinal chemist's perspective on the current understanding of DILI mechanisms, highlight cutting-edge assay developments for a holistic assessment, and discuss strategies for predicting DILI risks.

The team reviews hundreds of compounds from thousands of papers, press releases, and other sources each month to select candidates for Molecules of the Month. Here we have compiled a table of >70 additional molecules that were of interest in January 2024 along with highlights from some of our favorites, including molecules targeting SOS1, NLRP3, SMARCA2, and more.

This article highlights key patents published in September 2024, covering a range of therapeutic targets and mechanisms. It includes Nurr1 and Nur77 modulators for oncology applications, STAT3 inhibitors and CRBN-based STAT3 degraders for modulating STAT3 signaling in cancer, and CDK2 molecular glue degraders for estrogen receptor-positive breast cancer resistant to CDK4/CDK6 inhibitors. Additionally, it features ERAP1 modulators for addressing autoimmune diseases, APOL1 inhibitors for APOL1-mediated kidney diseases, and novel NEK7 inhibitors targeting the NLRP3 inflammasome pathway.

Genentech’s GDC-6599 is the first oral TRP Ankyrin 1 (TRPA1) antagonist to reach Ph. IIa (NCT05660850) for chronic cough after preclinical studies and a Ph. I trial showed it was well-tolerated, in contrast to prior molecules. The transient receptor potential (TRP) family of ion channels has been the subject of intensive drug discovery efforts due to their critical role in the development and progression of pain, itch, and respiratory conditions.