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Industrial applications of in silico ADMET

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Abstract

Quantitative structure activity relationship (QSAR) modeling has been in use for several decades now. One branch of it, in silico ADMET, became more and more important since the late 1990s as studies indicated that poor pharmacokinetics and toxicity were important causes of costly late-stage failures in drug development. In this paper we describe some of the available methods and best practice for the different stages of the in silico model building process. We also describe some more recent developments, like automated model building and the prediction probability. Finally we will discuss the use of in silico ADMET for “big data” and the importance and possible further development of interpretable models.

Schematic ADMET model generation process

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Acknowledgments

We want to thank our Colleagues from Computational Chemistry, Drug Discovery Support and Medicinal Chemistry. Several of the mentioned approaches have been established together with our colleagues from these departments. Without their continuous commitment, assistance and support most of the described research could have not been done.

B. Beck wants to thank Prof. T. Clark for the very good and productive time starting with the Diploma thesis followed by a PhD thesis and with a short intersection a 18 month PostDoc time.

T. Geppert wants to thank Prof. T. Clark for the productive collaborations since his time as a PhD candidate within Prof. G. Schneider’s lab at the ETH Zurich.

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Authors and Affiliations

  1. Department of Lead Identification and Optimization Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstrasse 65, 88397, Biberach an der Riss, Germany

    Bernd Beck & Tim Geppert

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  1. Bernd Beck
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  2. Tim Geppert
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Correspondence to Bernd Beck.

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This paper belongs to a Topical Collection on the occasion of Prof. Tim Clark’s 65th birthday

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Beck, B., Geppert, T. Industrial applications of in silico ADMET. J Mol Model 20, 2322 (2014). https://doi.org/10.1007/s00894-014-2322-5

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