Monitoring Global Growth of Activity Cliff Information over Time and Assessing Activity Cliff Frequencies and Distributions
Dagmar Stumpfe, Jürgen Bajorath · Future Medicinal Chemistry · 2015
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. CONCLUSION: 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.