Kinases are among the most important drug targets, yet the chemical matter explored against them remains surprisingly narrow. Conventional kinase-focused libraries are dominated by flat, heteroaromatic compounds, leaving saturated, three-dimensional molecules largely underexplored. This limited structural diversity can make it difficult to discover truly novel chemotypes, access alternative binding sites, and develop inhibitors with improved selectivity and drug-like properties.
In this webinar, Dr. Serghei Glinca, CEO of CrystalsFirst, will present a recent study investigating natural product-like fragments as a source of unconventional kinase-binding chemistry. Using a high-performance crystallographic soaking system for protein kinase A, the researchers resolved 36 fragment-bound structures at an hit rate of 41%. The fragments revealed diverse binding modes across the ATP and peripheral sites, including a previously unexplored allosteric binding opportunity and an unexpected protein conformational change. Cheminformatics analyses further demonstrated that these saturated, spatially complex fragments occupy a distinct chemical space compared with established kinase binders.
Serghei will share details of the crystallographic screening campaign, discuss the most intriguing protein–fragment complexes, and provide insights into how three-dimensional, natural product-like fragments can open new avenues for kinase drug discovery.
