A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk
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...
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| Veröffentlicht in: | MedChemComm 2022-02, Vol.13 (2), p.129-137 |
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| creator | Liu, Tao Beck, James P Hao, Junliang |
| description | 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.
The human pregnane X receptor (hPXR) regulates the expression of major drug metabolizing enzymes. |
| doi_str_mv | 10.1039/d1md00348h |
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The human pregnane X receptor (hPXR) regulates the expression of major drug metabolizing enzymes.</description><subject>Chemistry</subject><subject>Chemists</subject><subject>Drug development</subject><subject>Ligands</subject><subject>Literature reviews</subject><issn>2632-8682</issn><issn>2040-2503</issn><issn>2632-8682</issn><issn>2040-2511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNpVkdtLHDEYxUOpVFl96XvLQN-EqblMZpIXQbzDilJa6FvIJN_ORmcTTWa2dP96U1e361Mu58f5TnIQ-kzwd4KZPLJkYTFmlZh_QHu0ZrQUtaAft_a76CCle4wx5YTUXH5Cu4wzLDCVe2h1UpjgjUtQRFg6-FMEX8zvfv8oetdpb8sIJnTerZzvMpGcHSEVWSjSEEczjBHKVid4OesBOpflIRS677NdvlibZc0nbQa31IPLE6JLD_toZ6b7BAev6wT9ujj_eXpVTm8vr09PpqWpqBjKlkuoGsts1UpOQEtZa1rPKl0JLQkHXM9EwzHnUhCiLTQWCw21bhrcGloZNkHHa9_HsV2ANeBzml49RrfQ8a8K2qn3indz1YWlEqKuOGfZ4NurQQxP-fmDug9j9Dmzyp9MGilpQzJ1uKZMDClFmG0mEKz-VaXOyM3ZS1VXGf66nWmDvhWTgS9rICazUf93zZ4BXy2bQw</recordid><startdate>20220223</startdate><enddate>20220223</enddate><creator>Liu, Tao</creator><creator>Beck, James P</creator><creator>Hao, Junliang</creator><general>Royal Society of Chemistry</general><general>RSC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2480-6853</orcidid></search><sort><creationdate>20220223</creationdate><title>A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk</title><author>Liu, Tao ; Beck, James P ; Hao, Junliang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-b59e47d3d4b951ea996a26f4a48a915e06f8750559811ade7d08ae6a770bc24c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Chemistry</topic><topic>Chemists</topic><topic>Drug development</topic><topic>Ligands</topic><topic>Literature reviews</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Tao</creatorcontrib><creatorcontrib>Beck, James P</creatorcontrib><creatorcontrib>Hao, Junliang</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>MedChemComm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Tao</au><au>Beck, James P</au><au>Hao, Junliang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk</atitle><jtitle>MedChemComm</jtitle><addtitle>RSC Med Chem</addtitle><date>2022-02-23</date><risdate>2022</risdate><volume>13</volume><issue>2</issue><spage>129</spage><epage>137</epage><pages>129-137</pages><issn>2632-8682</issn><issn>2040-2503</issn><eissn>2632-8682</eissn><eissn>2040-2511</eissn><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.
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| fulltext | fulltext |
| identifier | ISSN: 2632-8682 |
| ispartof | MedChemComm, 2022-02, Vol.13 (2), p.129-137 |
| issn | 2632-8682 2040-2503 2632-8682 2040-2511 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8864553 |
| source | Royal Society Of Chemistry Journals; PubMed Central |
| subjects | Chemistry Chemists Drug development Ligands Literature reviews |
| title | A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk |
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