Systematic assessment of compound series with SAR transfer potential.

Compound series with different core structures that contain pairs of analogs with corresponding substitution patterns and similar activity represent structure-activity relationship (SAR) transfer events. On the basis of the matched molecular pair (MMP) formalism and linear regression analysis of compound potencies, a general approach is introduced for the identification of SAR transfer series (SAR-TS) and SAR-TS with regular potency progression (SAR-TS-RP). We have systematically extracted such series from public domain compound data and analyzed their size distribution and structural characteristics. More than 900 SAR-TS and 500 SAR-TS-RP with high-confidence potency annotations were identified in various compound activity classes. These series provide a substantial knowledge base for the analysis and prediction of SAR transfer and are made publicly available.