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A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk.

ABSTRACT: The human pregnane X receptor (hPXR) regulates the expression of major drug metabolizing enzymes. A wide range of drug candidates bind and activate hPXR, and hence are at risk of increasing drug-drug interactions and reducing clinical efficacy. hPXR structural features that function as hot spots for ligand binding are identified and highlighted in this concise review. Based on literature structure-activity relationship data as case studies, structure-based strategies to mitigate hPXR transactivation are summarized for medicinal chemists.

SUBMITTER: Liu T

PROVIDER: S-EPMC8864553 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk.

Liu Tao T Beck James P JP Hao Junliang J

RSC medicinal chemistry 20220119 2

The human pregnane X receptor (hPXR) regulates the expression of major drug metabolizing enzymes. A wide range of drug candidates bind and activate hPXR, and hence are at risk of increasing drug-drug interactions and reducing clinical efficacy. hPXR structural features that function as hot spots for ligand binding are identified and highlighted in this concise review. Based on literature structure-activity relationship data as case studies, structure-based strategies to mitigate hPXR transactiva ...[more]

PMID: 35308029

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