Monitoring global growth of activity cliff information over time and assessing activity cliff frequencies and distributions.
BACKGROUND
Activity cliffs (ACs) are formed by structurally analogous compounds with large potency variations. In medicinal chemistry, ACs are focal points of structure-activity relationship (SAR) analysis and typically studied on the basis of individual compound series.


RESULTS
ACs have been investigated on a large scale by analyzing active compounds from medicinal chemistry sources covering current pharmaceutical targets. Growth in AC populations has been determined and AC distributions have been analyzed.


CONCLUSIONS
Over the past few years, the number of available ACs has essentially doubled, which substantially expands the knowledge base for SAR exploration. However, the AC frequency, target distribution, and proportion of AC compounds have remained constant, thus providing a consistent picture of AC formation across bioactive compounds.
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology & Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr 2, D-53113 Bonn, Germany.
Dagmar
D
Stumpfe
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology & Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr 2, D-53113 Bonn, Germany.
Jürgen
J
Bajorath
D002626:Chemistry, Pharmaceutical / Q000379:methods; D062313:Databases, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations
SAR information; active compounds; activity cliff clusters; activity cliffs; compound data mining; rate of formation; target distribution; therapeutic targets