ReviewInformaticsThe many roles of molecular complexity in drug discovery

- Molecular complexity is used in lead optimization, library design and compound selection.
- Complexity as an intuitive concept but not easy to quantify in a unique manner.
- Topological, physicochemical, substructure and graph-based approaches have been used.

Molecular complexity is becoming a crucial concept in drug discovery. It has been associated with target selectivity, success in progressing into clinical development and compound safety, among other factors. Multiple metrics have been developed to quantify molecular complexity and explore complexity-property relationships. However, there is no general agreement regarding how to measure this molecular feature. Herein, we have surveyed the many roles of molecular complexity in drug discovery discussing in a critical manner different quantification methods. Through the analysis of various reference compound databases, common pitfalls and workarounds of the quantification of molecular complexity are discussed.

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