Conference by Prof. Dmitri KIREEV (University of Missouri, USA)

"Early-stage Discovery in the Era of Hard-to-Drug Targets and Giga-scale Chemical Spaces"

Contact: Prof. Alexandre VARNEK, Laboratory of Chemoinformatics

Abstract: Lead discovery is shifting toward hard-to-drug targets, while fast-growing chemical spaces offer new hit-finding opportunities. Yet, established technologies capable of effectively searching these vast chemical spaces for ligands to undruggable proteins are yet to emerge. We present our effort on addressing these challenges by enhancing our FRASE-based hit-finding robot (FRASE-bot) to include 3D pharmacophore searches on multi-billion datasets, Hit-Triage Pretrained Transformer (Hit-TPT), and ABFE simulations, as well as new strategies for extracting knowledge from phenotypic data, with a focus on lead identification and optimization. We exemplify the potential of the platform on several case studies including our winning participation in CACHE Challenges #1 and #2.