Data set of activity cliffs with single-atom modification and associated X-ray structure information for medicinal and computational chemistry applications

Activity cliffs (ACs) are defined as pairs of structurally similar or analogous active compounds with large potency differences [1]. As such, they provide important information for the exploration of structure-activity relationships (SARs) and chemical optimization. We have introduced a new category of ACs capturing minimal (single-atom) chemical modifications and identified more than 1500 of such ACs in compounds with activity against a variety of target proteins [2]. ACs with single-atom modifications (sam_ACs) include “atom-replacement ACs” (ar_ACs) that contain a single-atom replacement (N to C (N-C), O-C, N-O, or S-O) at a given position and “atom-walk ACs” (aw_ACs), in which two analogs are only distinguished by the position of a single heteroatom (non-carbon atom). For a number of sam_ACs, X-ray structures of complexes between AC targets and AC compounds were identified, which made it possible to explore the formation of sam_ACs on the basis of well-defined ligand-target interactions [2]. Our collection of sam_ACs including associated chemical and X-ray structure information, as described herein, is made freely available.