Design of a Highly Selective, Allosteric, Picomolar TYK2 Inhibitor in Clinical Development

Speakers

Craig E Masse
Former Head of Medicinal Chemistry at Nimbus Therapeutics
SVP, Discovery Research at Ajax Therapeutics

Sayan Mondal
Former Senior Director at Schrödinger Therapeutics Group

Abstract

In this webinar, we will highlight key moments from the discovery of this potentially best-in-class selective, allosteric, picomolar inhibitor of TYK2. This case study demonstrates various innovations in modeling to meet challenges over the course of the program, targeting both orthosteric and allosteric binding sites, including:

• The first application of large-scale free energy perturbation (FEP+) in drug discovery
• Extensive use of a novel physics-based method to predict solubility
• The first discovery of novel picomolar cores with FEP+

As these computationally-guided, structure-based discovery strategies are now increasingly deployed across industrial drug discovery projects, this program represents one of the first examples of the quality of the resulting end molecule as it moves through clinical trials.