Open Innovation for Phenotypic Drug Discovery: The PD2 Assay Panel
Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling...
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| Veröffentlicht in: | Journal of biomolecular screening 2011-07, Vol.16 (6), p.588-602 |
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| creator | Lee, Jonathan A. Chu, Shaoyou Willard, Francis S. Cox, Karen L. Sells Galvin, Rachelle J. Peery, Robert B. Oliver, Sarah E. Oler, Jennifer Meredith, Tamika D. Heidler, Steven A. Gough, Wendy H. Husain, Saba Palkowitz, Alan D. Moxham, Christopher M. |
| description | Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target “agnostic” fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD2), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD2 assay panel. Analysis of PD2 submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD2 have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD2, may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery. |
| doi_str_mv | 10.1177/1087057111405379 |
| format | Article |
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Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target “agnostic” fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD2), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD2 assay panel. Analysis of PD2 submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD2 have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD2, may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.</description><identifier>ISSN: 1087-0571</identifier><identifier>ISSN: 2472-5552</identifier><identifier>EISSN: 1552-454X</identifier><identifier>DOI: 10.1177/1087057111405379</identifier><identifier>PMID: 21521801</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Apolipoproteins E - metabolism ; Cell Cycle - drug effects ; Cell Differentiation - drug effects ; Cell Line ; Drug Discovery ; Drug Evaluation, Preclinical ; HeLa Cells ; Humans ; Insulin - metabolism ; Insulin Secretion ; Mice ; Neovascularization, Physiologic - drug effects ; Nocodazole - pharmacology ; Osteoblasts - cytology ; Osteoblasts - metabolism ; Phenotype ; Protein Kinase Inhibitors - pharmacology ; Rats ; Reproducibility of Results ; Signal Transduction - drug effects ; Tubulin Modulators - pharmacology ; Wnt Proteins - metabolism</subject><ispartof>Journal of biomolecular screening, 2011-07, Vol.16 (6), p.588-602</ispartof><rights>2011 Society for Laboratory Automation and Screening</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c340t-6e1a039688d3f89024c6e3fa97842cd75a10e020819055776cecae1e69471f423</citedby><cites>FETCH-LOGICAL-c340t-6e1a039688d3f89024c6e3fa97842cd75a10e020819055776cecae1e69471f423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21521801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Jonathan A.</creatorcontrib><creatorcontrib>Chu, Shaoyou</creatorcontrib><creatorcontrib>Willard, Francis S.</creatorcontrib><creatorcontrib>Cox, Karen L.</creatorcontrib><creatorcontrib>Sells Galvin, Rachelle J.</creatorcontrib><creatorcontrib>Peery, Robert B.</creatorcontrib><creatorcontrib>Oliver, Sarah E.</creatorcontrib><creatorcontrib>Oler, Jennifer</creatorcontrib><creatorcontrib>Meredith, Tamika D.</creatorcontrib><creatorcontrib>Heidler, Steven A.</creatorcontrib><creatorcontrib>Gough, Wendy H.</creatorcontrib><creatorcontrib>Husain, Saba</creatorcontrib><creatorcontrib>Palkowitz, Alan D.</creatorcontrib><creatorcontrib>Moxham, Christopher M.</creatorcontrib><title>Open Innovation for Phenotypic Drug Discovery: The PD2 Assay Panel</title><title>Journal of biomolecular screening</title><addtitle>J Biomol Screen</addtitle><description>Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target “agnostic” fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD2), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD2 assay panel. Analysis of PD2 submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD2 have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD2, may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.</description><subject>Animals</subject><subject>Apolipoproteins E - metabolism</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line</subject><subject>Drug Discovery</subject><subject>Drug Evaluation, Preclinical</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Mice</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Nocodazole - pharmacology</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - metabolism</subject><subject>Phenotype</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Reproducibility of Results</subject><subject>Signal Transduction - drug effects</subject><subject>Tubulin Modulators - pharmacology</subject><subject>Wnt Proteins - metabolism</subject><issn>1087-0571</issn><issn>2472-5552</issn><issn>1552-454X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1LAzEQxYMotlbvniQ3T6szm2ST9VZbPwqF9lDB2xK3s_2g3dRkt9D_3i2tHgTxNAPze483j7FrhDtEre8RjAalEVGCEjo9YW1UKo6kku-nzd6co_29xS5CWAKgSECes1aMKkYD2GaPow2VfFCWbmurhSt54Twfz6l01W6zyHnf1zPeX4TcbcnvHvhkTnzcj3k3BLvjY1vS6pKdFXYV6Oo4O-zt-WnSe42Go5dBrzuMciGhihJCCyJNjJmKwqQQyzwhUdhUGxnnU60sAkEMBlNQSuskp9wSUpJKjYWMRYfdHnw33n3WFKps3eSi1aoJ4eqQGSOg-Uvr_0mdSiPQ7Ek4kLl3IXgqso1frK3fZQjZvuLsd8WN5OZoXn-safoj-O60AaIDEOyMsqWrfdnU8rfhF2AKf_8</recordid><startdate>201107</startdate><enddate>201107</enddate><creator>Lee, Jonathan A.</creator><creator>Chu, Shaoyou</creator><creator>Willard, Francis S.</creator><creator>Cox, Karen L.</creator><creator>Sells Galvin, Rachelle J.</creator><creator>Peery, Robert B.</creator><creator>Oliver, Sarah E.</creator><creator>Oler, Jennifer</creator><creator>Meredith, Tamika D.</creator><creator>Heidler, Steven A.</creator><creator>Gough, Wendy H.</creator><creator>Husain, Saba</creator><creator>Palkowitz, Alan D.</creator><creator>Moxham, Christopher M.</creator><general>SAGE Publications</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>201107</creationdate><title>Open Innovation for Phenotypic Drug Discovery: The PD2 Assay Panel</title><author>Lee, Jonathan A. ; 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Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target “agnostic” fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD2), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD2 assay panel. Analysis of PD2 submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD2 have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD2, may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>21521801</pmid><doi>10.1177/1087057111405379</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1087-0571 |
| ispartof | Journal of biomolecular screening, 2011-07, Vol.16 (6), p.588-602 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Apolipoproteins E - metabolism Cell Cycle - drug effects Cell Differentiation - drug effects Cell Line Drug Discovery Drug Evaluation, Preclinical HeLa Cells Humans Insulin - metabolism Insulin Secretion Mice Neovascularization, Physiologic - drug effects Nocodazole - pharmacology Osteoblasts - cytology Osteoblasts - metabolism Phenotype Protein Kinase Inhibitors - pharmacology Rats Reproducibility of Results Signal Transduction - drug effects Tubulin Modulators - pharmacology Wnt Proteins - metabolism |
| title | Open Innovation for Phenotypic Drug Discovery: The PD2 Assay Panel |
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