11C-AZD4747 PET Brain-Penetration and Synthesis Update

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 November 2023 along with some highlights from some of our favorites below.

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.

Olutasidenib, discovered by Forma Therapeutics and marketed by Rigel, is an oral, brain-penetrant, selective mIDH1 inhibitor. It was granted Orphan Drug Designation and approved in December 2022 by the FDA for adults with relapsed/refractory acute myeloid leukemia. Approval was granted based on a Ph. I/II trial showing a 35% CR+CRh rate and a favorable 25.9-month median duration. This article describes the discovery and development of olutasidenib, how it is distinct from other mIDH inhibitors, and its potential in treating gliomas.

Gleevec (imatinib) was the first tyrosine kinase inhibitor approved for the treatment of cancer and one of the first products to emerge from "rational drug design."  It's invention changed chronic myeloid leukemia from an incurable death sentence to a manageable disease. Here's a look back on the tremendous value it's created over the last [...]

There were 16 acquisitions of companies with small molecule drug assets in 2021 and one merger. Here is a more in-depth look into all of the lead small molecules acquired in 2021, including a review of: The lead molecules in each acquisition and their structural representations where disclosed The mechanism of action, stage, and indication of [...]