Cytochrome P450s in the development of target-based anticancer drugs

Abstract Enzymes of the cytochrome P450 (CYP) superfamily are the major determinants of half-life and execute pharmacological effects of many therapeutic drugs. In new drug discovery research, recombinant (human) CYPs are also used for identifying active or inactive metabolites that could lead to in...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer letters 2008-01, Vol.259 (1), p.1-15
Hauptverfasser: Purnapatre, Kedar, Khattar, Sunil K, Saini, Kulvinder Singh
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 15
container_issue 1
container_start_page 1
container_title Cancer letters
container_volume 259
creator Purnapatre, Kedar
Khattar, Sunil K
Saini, Kulvinder Singh
description Abstract Enzymes of the cytochrome P450 (CYP) superfamily are the major determinants of half-life and execute pharmacological effects of many therapeutic drugs. In new drug discovery research, recombinant (human) CYPs are also used for identifying active or inactive metabolites that could lead to increased potency or toxicity of a molecule. In addition, CYP inhibition by anticancer drugs might lead to adverse drug reactions, multiple-drug resistance, and drug–drug interactions. During the discovery and pre-clinical evaluation of a New Chemical Entity (NCE), large amounts of purified recombinant CYPs are required for studying metabolism and pharmacokinetic parameters. Therefore, present research efforts are focused to over-express these human CYPs in bacteria, yeast, insect and mammalian cells, followed by their purification on an industrial scale to facilitate identification of novel anticancer drugs. This review summarizes the merits and limitations of these expression systems for an optimized production of individual CYP isoforms, and their usefulness in the discovery and development of target-based, safe and efficacious NCEs for the treatment of cancer.
doi_str_mv 10.1016/j.canlet.2007.10.024
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_21062983</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0304383507005095</els_id><sourcerecordid>3242048251</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-b58c23174070ed5e88fe0847c82a6502d6ba7a05b931d8e1c33fc13113a27be13</originalsourceid><addsrcrecordid>eNqFkVtrGzEQhUVpaNy0_6CUhULe1hndVvJLoThpUgi00PZZaKXZRO5eXEkb8L-vFhsCeenTwHDOmZlvCPlAYU2BNle7tbNjj3nNAFRprYGJV2RFtWK12mh4TVbAQdRcc3lO3qa0AwAplHxDzqkGyRuuV-R6e8iTe4zTgNUPISFVYazyI1Yen7Cf9gOOuZq6Ktv4gLlubUJf2TGHMtxhrHycH9I7ctbZPuH7U70gv7_e_Nre1fffb79tv9zXTihRzFI7xqkSoAC9RK07BC2U08w2EphvWqssyHbDqddIHeedo5xSbplqkfILcnnM3cfp74wpmyEkh31vR5zmZBiFhm00L8JPL4S7aY5j2c1QuUAQHJY4cVS5OKUUsTP7GAYbD4aCWRibnTkyNgvjpVsYF9vHU_jcDuifTSeoRfD5KMDC4ilgNMkFLLh8iOiy8VP434SXAa4PY0He_8EDpudbTGIGzM_lz8ubC1eQsJH8HzpkoXY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1505474301</pqid></control><display><type>article</type><title>Cytochrome P450s in the development of target-based anticancer drugs</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Purnapatre, Kedar ; Khattar, Sunil K ; Saini, Kulvinder Singh</creator><creatorcontrib>Purnapatre, Kedar ; Khattar, Sunil K ; Saini, Kulvinder Singh</creatorcontrib><description>Abstract Enzymes of the cytochrome P450 (CYP) superfamily are the major determinants of half-life and execute pharmacological effects of many therapeutic drugs. In new drug discovery research, recombinant (human) CYPs are also used for identifying active or inactive metabolites that could lead to increased potency or toxicity of a molecule. In addition, CYP inhibition by anticancer drugs might lead to adverse drug reactions, multiple-drug resistance, and drug–drug interactions. During the discovery and pre-clinical evaluation of a New Chemical Entity (NCE), large amounts of purified recombinant CYPs are required for studying metabolism and pharmacokinetic parameters. Therefore, present research efforts are focused to over-express these human CYPs in bacteria, yeast, insect and mammalian cells, followed by their purification on an industrial scale to facilitate identification of novel anticancer drugs. This review summarizes the merits and limitations of these expression systems for an optimized production of individual CYP isoforms, and their usefulness in the discovery and development of target-based, safe and efficacious NCEs for the treatment of cancer.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2007.10.024</identifier><identifier>PMID: 18053638</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - pharmacology ; Biotransformation ; Cancer ; Cloning, Molecular ; CYP ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Drug Design ; Drug discovery ; Drug Evaluation, Preclinical ; Drug Interactions ; Drug Resistance, Neoplasm ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacokinetics ; Enzyme Inhibitors - pharmacology ; Expression ; Genes ; Hematology, Oncology and Palliative Medicine ; Humans ; Isoenzymes - antagonists &amp; inhibitors ; Isoenzymes - metabolism ; Pharmaceutical industry ; Pharmacogenetics ; Pharmacokinetics ; Recombinant P450 ; Recombinant Proteins - antagonists &amp; inhibitors ; Recombinant Proteins - metabolism ; Reproducibility of Results ; Rodents</subject><ispartof>Cancer letters, 2008-01, Vol.259 (1), p.1-15</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2007 Elsevier Ireland Ltd</rights><rights>Copyright Elsevier Limited Jan 18, 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-b58c23174070ed5e88fe0847c82a6502d6ba7a05b931d8e1c33fc13113a27be13</citedby><cites>FETCH-LOGICAL-c474t-b58c23174070ed5e88fe0847c82a6502d6ba7a05b931d8e1c33fc13113a27be13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304383507005095$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18053638$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Purnapatre, Kedar</creatorcontrib><creatorcontrib>Khattar, Sunil K</creatorcontrib><creatorcontrib>Saini, Kulvinder Singh</creatorcontrib><title>Cytochrome P450s in the development of target-based anticancer drugs</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract Enzymes of the cytochrome P450 (CYP) superfamily are the major determinants of half-life and execute pharmacological effects of many therapeutic drugs. In new drug discovery research, recombinant (human) CYPs are also used for identifying active or inactive metabolites that could lead to increased potency or toxicity of a molecule. In addition, CYP inhibition by anticancer drugs might lead to adverse drug reactions, multiple-drug resistance, and drug–drug interactions. During the discovery and pre-clinical evaluation of a New Chemical Entity (NCE), large amounts of purified recombinant CYPs are required for studying metabolism and pharmacokinetic parameters. Therefore, present research efforts are focused to over-express these human CYPs in bacteria, yeast, insect and mammalian cells, followed by their purification on an industrial scale to facilitate identification of novel anticancer drugs. This review summarizes the merits and limitations of these expression systems for an optimized production of individual CYP isoforms, and their usefulness in the discovery and development of target-based, safe and efficacious NCEs for the treatment of cancer.</description><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biotransformation</subject><subject>Cancer</subject><subject>Cloning, Molecular</subject><subject>CYP</subject><subject>Cytochrome P-450 Enzyme Inhibitors</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Drug Design</subject><subject>Drug discovery</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Interactions</subject><subject>Drug Resistance, Neoplasm</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacokinetics</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Expression</subject><subject>Genes</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Isoenzymes - antagonists &amp; inhibitors</subject><subject>Isoenzymes - metabolism</subject><subject>Pharmaceutical industry</subject><subject>Pharmacogenetics</subject><subject>Pharmacokinetics</subject><subject>Recombinant P450</subject><subject>Recombinant Proteins - antagonists &amp; inhibitors</subject><subject>Recombinant Proteins - metabolism</subject><subject>Reproducibility of Results</subject><subject>Rodents</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVtrGzEQhUVpaNy0_6CUhULe1hndVvJLoThpUgi00PZZaKXZRO5eXEkb8L-vFhsCeenTwHDOmZlvCPlAYU2BNle7tbNjj3nNAFRprYGJV2RFtWK12mh4TVbAQdRcc3lO3qa0AwAplHxDzqkGyRuuV-R6e8iTe4zTgNUPISFVYazyI1Yen7Cf9gOOuZq6Ktv4gLlubUJf2TGHMtxhrHycH9I7ctbZPuH7U70gv7_e_Nre1fffb79tv9zXTihRzFI7xqkSoAC9RK07BC2U08w2EphvWqssyHbDqddIHeedo5xSbplqkfILcnnM3cfp74wpmyEkh31vR5zmZBiFhm00L8JPL4S7aY5j2c1QuUAQHJY4cVS5OKUUsTP7GAYbD4aCWRibnTkyNgvjpVsYF9vHU_jcDuifTSeoRfD5KMDC4ilgNMkFLLh8iOiy8VP434SXAa4PY0He_8EDpudbTGIGzM_lz8ubC1eQsJH8HzpkoXY</recordid><startdate>20080118</startdate><enddate>20080118</enddate><creator>Purnapatre, Kedar</creator><creator>Khattar, Sunil K</creator><creator>Saini, Kulvinder Singh</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20080118</creationdate><title>Cytochrome P450s in the development of target-based anticancer drugs</title><author>Purnapatre, Kedar ; Khattar, Sunil K ; Saini, Kulvinder Singh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-b58c23174070ed5e88fe0847c82a6502d6ba7a05b931d8e1c33fc13113a27be13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biotransformation</topic><topic>Cancer</topic><topic>Cloning, Molecular</topic><topic>CYP</topic><topic>Cytochrome P-450 Enzyme Inhibitors</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Drug Design</topic><topic>Drug discovery</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Interactions</topic><topic>Drug Resistance, Neoplasm</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacokinetics</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Expression</topic><topic>Genes</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Isoenzymes - antagonists &amp; inhibitors</topic><topic>Isoenzymes - metabolism</topic><topic>Pharmaceutical industry</topic><topic>Pharmacogenetics</topic><topic>Pharmacokinetics</topic><topic>Recombinant P450</topic><topic>Recombinant Proteins - antagonists &amp; inhibitors</topic><topic>Recombinant Proteins - metabolism</topic><topic>Reproducibility of Results</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Purnapatre, Kedar</creatorcontrib><creatorcontrib>Khattar, Sunil K</creatorcontrib><creatorcontrib>Saini, Kulvinder Singh</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Purnapatre, Kedar</au><au>Khattar, Sunil K</au><au>Saini, Kulvinder Singh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytochrome P450s in the development of target-based anticancer drugs</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2008-01-18</date><risdate>2008</risdate><volume>259</volume><issue>1</issue><spage>1</spage><epage>15</epage><pages>1-15</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract Enzymes of the cytochrome P450 (CYP) superfamily are the major determinants of half-life and execute pharmacological effects of many therapeutic drugs. In new drug discovery research, recombinant (human) CYPs are also used for identifying active or inactive metabolites that could lead to increased potency or toxicity of a molecule. In addition, CYP inhibition by anticancer drugs might lead to adverse drug reactions, multiple-drug resistance, and drug–drug interactions. During the discovery and pre-clinical evaluation of a New Chemical Entity (NCE), large amounts of purified recombinant CYPs are required for studying metabolism and pharmacokinetic parameters. Therefore, present research efforts are focused to over-express these human CYPs in bacteria, yeast, insect and mammalian cells, followed by their purification on an industrial scale to facilitate identification of novel anticancer drugs. This review summarizes the merits and limitations of these expression systems for an optimized production of individual CYP isoforms, and their usefulness in the discovery and development of target-based, safe and efficacious NCEs for the treatment of cancer.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18053638</pmid><doi>10.1016/j.canlet.2007.10.024</doi><tpages>15</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0304-3835
ispartof Cancer letters, 2008-01, Vol.259 (1), p.1-15
issn 0304-3835
1872-7980
language eng
recordid cdi_proquest_miscellaneous_21062983
source MEDLINE; Elsevier ScienceDirect Journals
subjects Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Biotransformation
Cancer
Cloning, Molecular
CYP
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Drug Design
Drug discovery
Drug Evaluation, Preclinical
Drug Interactions
Drug Resistance, Neoplasm
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacokinetics
Enzyme Inhibitors - pharmacology
Expression
Genes
Hematology, Oncology and Palliative Medicine
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - metabolism
Pharmaceutical industry
Pharmacogenetics
Pharmacokinetics
Recombinant P450
Recombinant Proteins - antagonists & inhibitors
Recombinant Proteins - metabolism
Reproducibility of Results
Rodents
title Cytochrome P450s in the development of target-based anticancer drugs
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T13%3A52%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytochrome%20P450s%20in%20the%20development%20of%20target-based%20anticancer%20drugs&rft.jtitle=Cancer%20letters&rft.au=Purnapatre,%20Kedar&rft.date=2008-01-18&rft.volume=259&rft.issue=1&rft.spage=1&rft.epage=15&rft.pages=1-15&rft.issn=0304-3835&rft.eissn=1872-7980&rft_id=info:doi/10.1016/j.canlet.2007.10.024&rft_dat=%3Cproquest_cross%3E3242048251%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1505474301&rft_id=info:pmid/18053638&rft_els_id=S0304383507005095&rfr_iscdi=true