Roles of the Chloro and Methoxy Groups in Drug Discovery

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.

Modern hit-finding technologies are incredible. Dean Brown and Jonas Bostrom at AstraZeneca have a very nice review out summarizing the hit-finding strategies for 66 clinical candidates published from 2016-2017. Some highlights include a clinical candidate from DNA-encoded libraries at GSK, the discovery of an RNA-binding drug candidate by [...]

Drug lipophilicity is a core property that contributes to drug solubility, permeability, metabolic disposition, and other key properties. Increasing lipophilicity can often lead to increased affinity in relevant biological assays due to the hydrophobic nature of many protein binding pockets,  but this may also increase promiscuity to [...]

The real magic happens when chemists can integrate computational models into their assay cascades, thanks to trust in their predictions. To get there, grounding computational predictions in physics and experimental reality makes all the difference. In this article, Abba E. Leffler, Ph.D. from Schrödinger tells us about: How to make [...]

Functional groups that medicinal chemists don't encounter regularly often face greater scrutiny compared to more common ones. In his Flash Talk, Gilles Ouvry challenges these biases and presents data on four uncommon functional groups that required extra convincing to gain acceptance. Here we supply a PDF download of his slides for our members.