Molecular similarity in chemical informatics and predictive toxicity modeling: from quantitative read-across (q-RA) to quantitative read-across structure-activity relationship (q-RASAR) with the application of machine learning.

Journal: Critical reviews in toxicology
PMID: 39225123

Abstract

This article aims to provide a comprehensive critical, yet readable, review of general interest to the chemistry community on molecular similarity as applied to chemical informatics and predictive modeling with a special focus on read-across (RA) and read-across structure-activity relationships (RASAR). Molecular similarity-based computational tools, such as quantitative structure-activity relationships (QSARs) and RA, are routinely used to fill the data gaps for a wide range of properties including toxicity endpoints for regulatory purposes. This review will explore the background of RA starting from how structural information has been used through to how other similarity contexts such as physicochemical, absorption, distribution, metabolism, and elimination (ADME) properties, and biological aspects are being characterized. More recent developments of RA's integration with QSAR have resulted in the emergence of novel models such as ToxRead, generalized read-across (GenRA), and quantitative RASAR (q-RASAR). Conventional QSAR techniques have been excluded from this review except where necessary for context.

Authors

  • Arkaprava Banerjee
    Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
  • Supratik Kar
    Chemometrics and Molecular Modeling Laboratory, Department of Chemistry and Physics, Kean University, Union, NJ, USA.
  • Kunal Roy
    Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
  • Grace Patlewicz
    National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, Durham, North Carolina 27711, United States.
  • Nathaniel Charest
    Department of Chemistry and Biochemistry , University of California Santa Barbara , Santa Barbara , California 93106-9510 , United States.
  • Emilio Benfenati
    Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via Giuseppe La Masa 19, 20156 Milan, Italy.
  • Mark T D Cronin
    School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom.

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