Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits
We herein outline the usefulness of drug-like screening hits. As for lead-like hits it is of pivotal importance to have a detailed profile with experimental data prior to initiating costly and resource-intense lead optimization programs. Drug-like and lead-like hits derived from HTS campaigns provid...
Gespeichert in:
| Veröffentlicht in: | Drug discovery today 2006-02, Vol.11 (3-4), p.175-180 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 180 |
|---|---|
| container_issue | 3-4 |
| container_start_page | 175 |
| container_title | Drug discovery today |
| container_volume | 11 |
| creator | Wunberg, Tobias Hendrix, Martin Hillisch, Alexander Lobell, Mario Meier, Heinrich Schmeck, Carsten Wild, Hanno Hinzen, Berthold |
| description | We herein outline the usefulness of drug-like screening hits. As for lead-like hits it is of pivotal importance to have a detailed profile with experimental data prior to initiating costly and resource-intense lead optimization programs.
Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME–Tox) profiling is needed to help identify hits with a minimum number of (known) liabilities. This is particularly true for drug-like hits. Herein, we describe how to break down large numbers of screening hits and we provide a comprehensive overview of the strengths and weaknesses for each structural class. The overall profile (e.g. ligand efficiency, selectivity and ADME–Tox) is the distinctive feature that will define the priority for follow-up. |
| doi_str_mv | 10.1016/S1359-6446(05)03700-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17108793</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1359644605037001</els_id><sourcerecordid>17108793</sourcerecordid><originalsourceid>FETCH-LOGICAL-c424t-117b4c85e54d35143d65375efc0e4fc4835aabe55a708ee6b3836f31a98b31143</originalsourceid><addsrcrecordid>eNqFkE1vFSEUhkmjaWvtT2jDRqMLlHOBgduNMY0fTZq40K4JA2da7Hy0nLk38d_L9F7TpSvg5HkPbx7GzkB-AAnNx5-gzFo0WjfvpHkvlZVSwAE7BmedME6tXtT7P-SIvSL6LSWs1qY5ZEfQGKUsNMcsXg0PZdrm8ZbPd8jv8izmSfQYEq_ziEQXPIU5iFTyFkceiOpswHHmU8dT2dyKPt8jD2PiS2r3olgQx2VpXUiv2csu9ISn-_OE3Xz98uvyu7j-8e3q8vO1iHqlZwFgWx2dQaOTMqBVqi2twS5K1F3UTpkQWjQmWOkQm1Y51XQKwtq1Cip_wt7u9tbmjxuk2Q-ZIvZ9GHHakAcL0tm1qqDZgbFMRAU7_1DyEMofD9Ivdv2TXb-o89L4J7seau58_8GmHTA9p_Y6K_BmDwSKoe9KGGOmZ85q68xqKfBpx2HVsc1YPMWMY8SUC8bZpyn_p8pfdouWgw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17108793</pqid></control><display><type>article</type><title>Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Wunberg, Tobias ; Hendrix, Martin ; Hillisch, Alexander ; Lobell, Mario ; Meier, Heinrich ; Schmeck, Carsten ; Wild, Hanno ; Hinzen, Berthold</creator><creatorcontrib>Wunberg, Tobias ; Hendrix, Martin ; Hillisch, Alexander ; Lobell, Mario ; Meier, Heinrich ; Schmeck, Carsten ; Wild, Hanno ; Hinzen, Berthold</creatorcontrib><description>We herein outline the usefulness of drug-like screening hits. As for lead-like hits it is of pivotal importance to have a detailed profile with experimental data prior to initiating costly and resource-intense lead optimization programs.
Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME–Tox) profiling is needed to help identify hits with a minimum number of (known) liabilities. This is particularly true for drug-like hits. Herein, we describe how to break down large numbers of screening hits and we provide a comprehensive overview of the strengths and weaknesses for each structural class. The overall profile (e.g. ligand efficiency, selectivity and ADME–Tox) is the distinctive feature that will define the priority for follow-up.</description><identifier>ISSN: 1359-6446</identifier><identifier>EISSN: 1878-5832</identifier><identifier>DOI: 10.1016/S1359-6446(05)03700-1</identifier><identifier>PMID: 16533716</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>ADME-Tox ; Administration, Oral ; Biological and medical sciences ; Drug Design ; General pharmacology ; hit-to-lead process ; hits ; HTS ; leads ; Medical sciences ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacokinetics ; Pharmacology. Drug treatments ; Toxicology</subject><ispartof>Drug discovery today, 2006-02, Vol.11 (3-4), p.175-180</ispartof><rights>2006 Elsevier Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-117b4c85e54d35143d65375efc0e4fc4835aabe55a708ee6b3836f31a98b31143</citedby><cites>FETCH-LOGICAL-c424t-117b4c85e54d35143d65375efc0e4fc4835aabe55a708ee6b3836f31a98b31143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1359644605037001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17478523$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16533716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wunberg, Tobias</creatorcontrib><creatorcontrib>Hendrix, Martin</creatorcontrib><creatorcontrib>Hillisch, Alexander</creatorcontrib><creatorcontrib>Lobell, Mario</creatorcontrib><creatorcontrib>Meier, Heinrich</creatorcontrib><creatorcontrib>Schmeck, Carsten</creatorcontrib><creatorcontrib>Wild, Hanno</creatorcontrib><creatorcontrib>Hinzen, Berthold</creatorcontrib><title>Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits</title><title>Drug discovery today</title><addtitle>Drug Discov Today</addtitle><description>We herein outline the usefulness of drug-like screening hits. As for lead-like hits it is of pivotal importance to have a detailed profile with experimental data prior to initiating costly and resource-intense lead optimization programs.
Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME–Tox) profiling is needed to help identify hits with a minimum number of (known) liabilities. This is particularly true for drug-like hits. Herein, we describe how to break down large numbers of screening hits and we provide a comprehensive overview of the strengths and weaknesses for each structural class. The overall profile (e.g. ligand efficiency, selectivity and ADME–Tox) is the distinctive feature that will define the priority for follow-up.</description><subject>ADME-Tox</subject><subject>Administration, Oral</subject><subject>Biological and medical sciences</subject><subject>Drug Design</subject><subject>General pharmacology</subject><subject>hit-to-lead process</subject><subject>hits</subject><subject>HTS</subject><subject>leads</subject><subject>Medical sciences</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Toxicology</subject><issn>1359-6446</issn><issn>1878-5832</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1vFSEUhkmjaWvtT2jDRqMLlHOBgduNMY0fTZq40K4JA2da7Hy0nLk38d_L9F7TpSvg5HkPbx7GzkB-AAnNx5-gzFo0WjfvpHkvlZVSwAE7BmedME6tXtT7P-SIvSL6LSWs1qY5ZEfQGKUsNMcsXg0PZdrm8ZbPd8jv8izmSfQYEq_ziEQXPIU5iFTyFkceiOpswHHmU8dT2dyKPt8jD2PiS2r3olgQx2VpXUiv2csu9ISn-_OE3Xz98uvyu7j-8e3q8vO1iHqlZwFgWx2dQaOTMqBVqi2twS5K1F3UTpkQWjQmWOkQm1Y51XQKwtq1Cip_wt7u9tbmjxuk2Q-ZIvZ9GHHakAcL0tm1qqDZgbFMRAU7_1DyEMofD9Ivdv2TXb-o89L4J7seau58_8GmHTA9p_Y6K_BmDwSKoe9KGGOmZ85q68xqKfBpx2HVsc1YPMWMY8SUC8bZpyn_p8pfdouWgw</recordid><startdate>20060201</startdate><enddate>20060201</enddate><creator>Wunberg, Tobias</creator><creator>Hendrix, Martin</creator><creator>Hillisch, Alexander</creator><creator>Lobell, Mario</creator><creator>Meier, Heinrich</creator><creator>Schmeck, Carsten</creator><creator>Wild, Hanno</creator><creator>Hinzen, Berthold</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20060201</creationdate><title>Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits</title><author>Wunberg, Tobias ; Hendrix, Martin ; Hillisch, Alexander ; Lobell, Mario ; Meier, Heinrich ; Schmeck, Carsten ; Wild, Hanno ; Hinzen, Berthold</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-117b4c85e54d35143d65375efc0e4fc4835aabe55a708ee6b3836f31a98b31143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>ADME-Tox</topic><topic>Administration, Oral</topic><topic>Biological and medical sciences</topic><topic>Drug Design</topic><topic>General pharmacology</topic><topic>hit-to-lead process</topic><topic>hits</topic><topic>HTS</topic><topic>leads</topic><topic>Medical sciences</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wunberg, Tobias</creatorcontrib><creatorcontrib>Hendrix, Martin</creatorcontrib><creatorcontrib>Hillisch, Alexander</creatorcontrib><creatorcontrib>Lobell, Mario</creatorcontrib><creatorcontrib>Meier, Heinrich</creatorcontrib><creatorcontrib>Schmeck, Carsten</creatorcontrib><creatorcontrib>Wild, Hanno</creatorcontrib><creatorcontrib>Hinzen, Berthold</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Drug discovery today</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wunberg, Tobias</au><au>Hendrix, Martin</au><au>Hillisch, Alexander</au><au>Lobell, Mario</au><au>Meier, Heinrich</au><au>Schmeck, Carsten</au><au>Wild, Hanno</au><au>Hinzen, Berthold</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits</atitle><jtitle>Drug discovery today</jtitle><addtitle>Drug Discov Today</addtitle><date>2006-02-01</date><risdate>2006</risdate><volume>11</volume><issue>3-4</issue><spage>175</spage><epage>180</epage><pages>175-180</pages><issn>1359-6446</issn><eissn>1878-5832</eissn><abstract>We herein outline the usefulness of drug-like screening hits. As for lead-like hits it is of pivotal importance to have a detailed profile with experimental data prior to initiating costly and resource-intense lead optimization programs.
Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME–Tox) profiling is needed to help identify hits with a minimum number of (known) liabilities. This is particularly true for drug-like hits. Herein, we describe how to break down large numbers of screening hits and we provide a comprehensive overview of the strengths and weaknesses for each structural class. The overall profile (e.g. ligand efficiency, selectivity and ADME–Tox) is the distinctive feature that will define the priority for follow-up.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>16533716</pmid><doi>10.1016/S1359-6446(05)03700-1</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-6446 |
| ispartof | Drug discovery today, 2006-02, Vol.11 (3-4), p.175-180 |
| issn | 1359-6446 1878-5832 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17108793 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | ADME-Tox Administration, Oral Biological and medical sciences Drug Design General pharmacology hit-to-lead process hits HTS leads Medical sciences Pharmaceutical technology. Pharmaceutical industry Pharmacokinetics Pharmacology. Drug treatments Toxicology |
| title | Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T01%3A59%3A50IST&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=Improving%20the%20hit-to-lead%20process:%20data-driven%20assessment%20of%20drug-like%20and%20lead-like%20screening%20hits&rft.jtitle=Drug%20discovery%20today&rft.au=Wunberg,%20Tobias&rft.date=2006-02-01&rft.volume=11&rft.issue=3-4&rft.spage=175&rft.epage=180&rft.pages=175-180&rft.issn=1359-6446&rft.eissn=1878-5832&rft_id=info:doi/10.1016/S1359-6446(05)03700-1&rft_dat=%3Cproquest_cross%3E17108793%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=17108793&rft_id=info:pmid/16533716&rft_els_id=S1359644605037001&rfr_iscdi=true |