Computer systems for the prediction of xenobiotic metabolism
Abstract
The aim of pharmaceutical research and development is to ensure a continuing pipeline of new chemical entities (NCEs) displaying high therapeutic efficacy with few or no side effects. Failure of promising lead candidates late in the drug discovery processes is regarded as commercially unacceptable in today's increasingly competitive business environment. An inappropriate ADME/Toxicity profile in humans is the major cause of failure of lead candidates in late clinical stages of drug development. Combinatorial chemistry techniques coupled with high throughput screening protocols means that pharmaceutical companies are now dealing with an unprecedented number of NCEs on an annual basis. As a consequence, screening for undesirable ADME/Toxicity properties in the early stages of drug development, preferably pre-synthesis, is now considered the essential paradigm. In silico assessment of NCEs is rapidly emerging as the next wave of technology for early ADME/Toxicity prediction. In this review, we discuss the major commercially available products for the assessing the potential metabolic activity of xenobiotic substances in mammalian systems.
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More than 300 empirical rules allow prediction of the fate of metabolites based on their chemical structure.
“In fact, there are .300different empirical rules that allow one to predict the fate of metabolites on the basis of their chemical structure (69).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [69]
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- Authors
- Langowski, J., & Long, A.
- Affiliations
- University of Leeds (GB)
- Corresponding author
- Long, Anthony
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 54
- Issue
- 3
- Pages
- 407-415
- ISSN
- 0169-409X (ISSN-L)
- OpenAlex
- W2044694490
- Cited by
- 138
- References
- 23
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 8 · 2012: 4
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- new chemical entities, drug discovery, mammalian metabolism, computer-aided drug design, toxicity prediction
- MeSH terms
- Animals, Computers, Enzymes, Expert Systems, Humans, Models, Molecular, Predictive Value of Tests, Xenobiotics, Databases, Factual, Computational Biology
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