Small Molecules Evolve

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.

One of the key challenges in CNS projects is achieving sufficient unbound brain exposure to engage the target. To predict CNS exposure, scientists employ metrics like CNS MPO scores from Pfizer and Merck, Bayesian models, and methods for balancing physicochemical properties. However, these in silico metrics often fail to correlate well with experimental data. Schrödinger's team has discovered the energy of solvation (E-sol) metric, which accurately predicts Kp,uu and has been validated with CNS-penetrant DLK inhibitors. Explore more in this detailed Drug Hunter article.

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. In this 4-part series we will give you an open-access overview of the M&A landscape, and then for Drug Hunter members in the coming weeks, we will be providing in-depth coverage and analysis of the small molecule-focused (parts 2 & 3) and biologics-based deals (part 4). This premium content includes background on the targets, chemical/biological matter and clinical data driving these deals.

The "New Drugs on the Horizon" sessions at the AACR Annual Meeting 2024 in San Diego revealed twelve innovative oncology agents and offered attendees a first look at their structures and preliminary data as they enter/progress in the clinic. In case you missed any of these exciting compounds – including selective CDK inhibitors, molecular glues, bifunctional degraders, a radiopharmaceutical, a bifunctional antibody, and an ADC – this article covers the structures and targets disclosed. A separate session disclosed the structure of a pan-RAS isoform inhibitor with remarkable clinical results.

In this Flash Talk, Yoshihiro Ishihara discussed the beneficial effects of chloro and methoxy substituents on intermolecular interactions, as well as the unique advantages and disadvantages of employing these substituents in drug discovery.

As part of our Flash Talk webinar series, we present a PDF of Yoshihiro Ishihara's slide deck and full text questions and answers from his talk, entitled "Roles of the Chloro and Methoxy Groups in Drug Discovery." Check out the recording of the talk on our Drug Hunter YouTube channel.