Bayer's in silico ADMET platform: a journey of machine learning over the past two decades.

Journal: Drug discovery today
PMID:

Abstract

Over the past two decades, an in silico absorption, distribution, metabolism, and excretion (ADMET) platform has been created at Bayer Pharma with the goal to generate models for a variety of pharmacokinetic and physicochemical endpoints in early drug discovery. These tools are accessible to all scientists within the company and can be a useful in assisting with the selection and design of novel leads, as well as the process of lead optimization. Here. we discuss the development of machine-learning (ML) approaches with special emphasis on data, descriptors, and algorithms. We show that high company internal data quality and tailored descriptors, as well as a thorough understanding of the experimental endpoints, are essential to the utility of our models. We discuss the recent impact of deep neural networks and show selected application examples.

Authors

  • Andreas H Göller
    Bayer AG, Pharmaceuticals, R&D, Computational Molecular Design, 42096 Wuppertal, Germany.
  • Lara Kuhnke
    Bayer HealthCare, Berlin, Germany.
  • Floriane Montanari
    Department of Bioinformatics , Bayer AG , Berlin , Germany . Email: robin.winter@bayer.com.
  • Anne Bonin
    Bayer AG, Pharmaceuticals, R&D, Computational Molecular Design, 42096 Wuppertal, Germany.
  • Sebastian Schneckener
    Bayer AG, Engineering & Technology, Applied Mathematics, 51368 Leverkusen, Germany.
  • Antonius Ter Laak
    Bayer AG, Pharmaceuticals, R&D, Computational Molecular Design, 13342 Berlin, Germany.
  • Jörg Wichard
    Bayer AG, Pharmaceuticals, R&D, Genetic Toxicology, 13342 Berlin, Germany.
  • Mario Lobell
    Bayer AG, Pharmaceuticals, R&D, Computational Molecular Design, 42096 Wuppertal, Germany.
  • Alexander Hillisch
    Bayer AG , Drug Discovery, Chemical Research , 42096 Wuppertal , Germany.