Abstract
Cytochrome P450 (CYP450) has widely been implicated for drug-drug interactions (DDI) in the pharmaceutical industry. Inhibition or induction of this enzyme family has led to withdrawal of multiple drugs from the market leading to major time and financial losses for the pharmaceutical industry. CYP450 plays a prevailing role in the biotransformation of a large number of structurally diverse drugs. Few isoenzymes of the CYP enzyme family (CYP3A4, 2D6 and 2C9 family) are mainly involved in metabolism of most of the drugs. To avoid such interactions and potentially minimize DDI, major pharmaceutical organizations prefer to incorporate CYP enzyme screening at an early stage of their discovery program. While this has been a prevalent practice in the pharmaceutical industry lately, there is very limited literature available reviewing the relationship between chemotypes and CYP isoforms. This review will collate literature pertaining to CYP-inhibition modulation through physicochemical parameters and chemical modification and thus bring to focus commonly used trends by medicinal chemists world-wide.
Keywords: Cytochrome-P450, CYP inhibition, drug discovery, physicochemical properties, heterocylic compounds, chemical modification, structure-activity relationship, medicinal chemistry
Current Medicinal Chemistry
Title:Modulation of Cytochrome-P450 Inhibition (CYP) in Drug Discovery: A Medicinal Chemistry Perspective
Volume: 19 Issue: 21
Author(s): Sanjay Kumar, Rajiv Sharma and Abhijit Roychowdhury
Affiliation:
Keywords: Cytochrome-P450, CYP inhibition, drug discovery, physicochemical properties, heterocylic compounds, chemical modification, structure-activity relationship, medicinal chemistry
Abstract: Cytochrome P450 (CYP450) has widely been implicated for drug-drug interactions (DDI) in the pharmaceutical industry. Inhibition or induction of this enzyme family has led to withdrawal of multiple drugs from the market leading to major time and financial losses for the pharmaceutical industry. CYP450 plays a prevailing role in the biotransformation of a large number of structurally diverse drugs. Few isoenzymes of the CYP enzyme family (CYP3A4, 2D6 and 2C9 family) are mainly involved in metabolism of most of the drugs. To avoid such interactions and potentially minimize DDI, major pharmaceutical organizations prefer to incorporate CYP enzyme screening at an early stage of their discovery program. While this has been a prevalent practice in the pharmaceutical industry lately, there is very limited literature available reviewing the relationship between chemotypes and CYP isoforms. This review will collate literature pertaining to CYP-inhibition modulation through physicochemical parameters and chemical modification and thus bring to focus commonly used trends by medicinal chemists world-wide.
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Cite this article as:
Kumar Sanjay, Sharma Rajiv and Roychowdhury Abhijit, Modulation of Cytochrome-P450 Inhibition (CYP) in Drug Discovery: A Medicinal Chemistry Perspective, Current Medicinal Chemistry 2012; 19 (21) . https://dx.doi.org/10.2174/092986712801323180
DOI https://dx.doi.org/10.2174/092986712801323180 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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