Issue 5, 2023

Alchemical analysis of FDA approved drugs


Chemical space maps help visualize similarities within molecular sets. However, there are many different molecular similarity measures resulting in a confusing number of possible comparisons. To overcome this limitation, we exploit the fact that tools designed for reaction informatics also work for alchemical processes that do not obey Lavoisier's principle, such as the transmutation of lead into gold. We start by using the differential reaction fingerprint (DRFP) to create tree-maps (TMAPs) representing the chemical space of pairs of drugs selected as being similar according to various molecular fingerprints. We then use the Transformer-based RXNMapper model to understand structural relationships between drugs, and its confidence score to distinguish between pairs related by chemically feasible transformations and pairs related by alchemical transmutations. This analysis reveals a diversity of structural similarity relationships that are otherwise difficult to analyze simultaneously. We exemplify this approach by visualizing FDA-approved drugs, EGFR inhibitors, and polymyxin B analogs.

Graphical abstract: Alchemical analysis of FDA approved drugs

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Article information

Article type
14 Mar 2023
29 Aug 2023
First published
30 Aug 2023
This article is Open Access
Creative Commons BY license

Digital Discovery, 2023,2, 1289-1296

Alchemical analysis of FDA approved drugs

M. Orsi, D. Probst, P. Schwaller and J. Reymond, Digital Discovery, 2023, 2, 1289 DOI: 10.1039/D3DD00039G

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