Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools

Title:Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools

Volume: 18 Issue: 6

Author(s): Naiem T. Issa, Henri Wathieu, Abiola Ojo, Stephen W. Byers and Sivanesan Dakshanamurthy*

Affiliation:

• Georgetown-Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington DC, 20057,United States

Keywords: Preclinical drug development, computational tools, in silico prediction, drug-target signatures, toxicology.

Abstract: Background: While establishing efficacy in translational models and humans through clinically-relevant endpoints for disease is of great interest, assessing the potential toxicity of a putative therapeutic drug is critical. Toxicological assessments in the pre-clinical discovery phase help to avoid future failure in the clinical phases of drug development. Many in vitro assays exist to aid in modular toxicological assessment, such as hepatotoxicity and genotoxicity. While these methods have provided tremendous insight into human toxicity by investigational new drugs, they are expensive, require substantial resources, and do not account for pharmacogenomics as well as critical ADME properties. Computational tools can fill this niche in toxicology if in silico models are accurate in relating drug molecular properties to toxicological endpoints as well as reliable in predicting important drug-target interactions that mediate known adverse events or adverse outcome pathways (AOPs).

Methods: We undertook an unstructured search of multiple bibliographic databases for peer-reviewed literature regarding computational methods in predictive toxicology for in silico drug discovery. As this review paper is meant to serve as a survey of available methods for the interested reader, no focused criteria were applied. Literature chosen was based on the writers’ expertise and intent in communicating important aspects of in silico toxicology to the interested reader.

Conclusion: This review provides a purview of computational methods of pre-clinical toxicologic assessments for novel small molecule drugs that may be of use for novice and experienced investigators as well as academic and commercial drug discovery entities.

Cite this article as:

Issa T. Naiem, Wathieu Henri , Ojo Abiola , Byers W. Stephen and Dakshanamurthy Sivanesan *, Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools, Current Drug Metabolism 2017; 18 (6) . https://dx.doi.org/10.2174/1389200218666170316093301

DOI https://dx.doi.org/10.2174/1389200218666170316093301	Print ISSN 1389-2002
Publisher Name Bentham Science Publisher	Online ISSN 1875-5453