Cover Feature: An Internal Sulfur–Lone Pair Interaction Enabled the Discovery of Potent and Sub‐Family Selective PKMYT1 Inhibitors (ChemMedChem 6/2026)

This study reports the discovery of a novel class of potent and selective PKMYT1 inhibitors enabled by the deliberate exploitation of an intramolecular sulfur–lone pair interaction. By assistance of AI-powered generative chemistry, comprehensive SAR analysis, and structure guided optimization, a thiazole based scaffold was identified that enforces a near coplanar conformation. The lead compound A4 with favorable structural novelty exhibits strong PKMYT1 potency, high selectivity over WEE1, and potential drug-like properties. This work highlights the utility of nonclassical intramolecular interactions as an effective strategy in kinase inhibitor design. More details can be found in the Research Article by Xiao Ding, Alex Zhavoronkov, and co-workers (DOI: 10.1002/cmdc.202501029).