Systematic identification of target set-dependent activity cliffs

Abstract

Aim: Generating a knowledge base of new activity cliffs (ACs) defined on the basis of compound set-dependent potency distributions, also taking confirmed inactive compounds into account. Methodology: Different AC definitions, representations and search criteria were rationalized and applied. Data: For nearly 100 different target proteins, for which medicinal chemistry and biological screening data were available, target set-dependent ACs were identified. More than 20,000 target set-dependent ACs and associated information are made freely available. Limitations & next steps: As more compound data become available for new targets, the search for target set-dependent ACs, including confirmed inactive compounds will continue. Second-generation ACs will be subjected to systematic structure-activity relationship analysis.