Label-free target identification in drug discovery via phenotypic screening
[Display omitted] Phenotypic screening has demonstrated its advantage in the discovery of first-in-class therapeutics, whereas target-based screening has showed strength for follower drugs. Owing to the unbiased nature of phenotypic screening, novel druggable proteins can be uncovered by target iden...
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| Veröffentlicht in: | Current opinion in chemical biology 2019-06, Vol.50, p.66-72 |
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| container_title | Current opinion in chemical biology |
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| creator | Park, Hankum Ha, Jaeyoung Park, Seung Bum |
| description | [Display omitted]
Phenotypic screening has demonstrated its advantage in the discovery of first-in-class therapeutics, whereas target-based screening has showed strength for follower drugs. Owing to the unbiased nature of phenotypic screening, novel druggable proteins can be uncovered by target identification. Chemical label-free target identification methods can eliminate the functionalization step of an original bioactive compound. Herein, we summarize recent advances in the development of label-free target identification methods, which are based on changes in protein stability against proteolysis, and chemical and thermal denaturation. Owing to the increasing application of shift in thermal stability for protein analysis in live cells and tissues, we mainly focus on the cellular stability shift assay and its proteome-wide application for target identification. |
| doi_str_mv | 10.1016/j.cbpa.2019.02.006 |
| format | Article |
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Phenotypic screening has demonstrated its advantage in the discovery of first-in-class therapeutics, whereas target-based screening has showed strength for follower drugs. Owing to the unbiased nature of phenotypic screening, novel druggable proteins can be uncovered by target identification. Chemical label-free target identification methods can eliminate the functionalization step of an original bioactive compound. Herein, we summarize recent advances in the development of label-free target identification methods, which are based on changes in protein stability against proteolysis, and chemical and thermal denaturation. Owing to the increasing application of shift in thermal stability for protein analysis in live cells and tissues, we mainly focus on the cellular stability shift assay and its proteome-wide application for target identification.</description><identifier>ISSN: 1367-5931</identifier><identifier>EISSN: 1879-0402</identifier><identifier>DOI: 10.1016/j.cbpa.2019.02.006</identifier><identifier>PMID: 30933868</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Drug Discovery ; Electrophoresis, Gel, Two-Dimensional ; Oxidation-Reduction ; Phenotype ; Protein Denaturation ; Protein Stability ; Proteolysis ; Proteome ; Small Molecule Libraries ; Temperature</subject><ispartof>Current opinion in chemical biology, 2019-06, Vol.50, p.66-72</ispartof><rights>2019</rights><rights>Copyright © 2019. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-91fd635675a58f974e3762567a7e35a2e59d9e4675aac5f3db6fe21d86e16bc13</citedby><cites>FETCH-LOGICAL-c356t-91fd635675a58f974e3762567a7e35a2e59d9e4675aac5f3db6fe21d86e16bc13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1367593118301716$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30933868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Hankum</creatorcontrib><creatorcontrib>Ha, Jaeyoung</creatorcontrib><creatorcontrib>Park, Seung Bum</creatorcontrib><title>Label-free target identification in drug discovery via phenotypic screening</title><title>Current opinion in chemical biology</title><addtitle>Curr Opin Chem Biol</addtitle><description>[Display omitted]
Phenotypic screening has demonstrated its advantage in the discovery of first-in-class therapeutics, whereas target-based screening has showed strength for follower drugs. Owing to the unbiased nature of phenotypic screening, novel druggable proteins can be uncovered by target identification. Chemical label-free target identification methods can eliminate the functionalization step of an original bioactive compound. Herein, we summarize recent advances in the development of label-free target identification methods, which are based on changes in protein stability against proteolysis, and chemical and thermal denaturation. Owing to the increasing application of shift in thermal stability for protein analysis in live cells and tissues, we mainly focus on the cellular stability shift assay and its proteome-wide application for target identification.</description><subject>Drug Discovery</subject><subject>Electrophoresis, Gel, Two-Dimensional</subject><subject>Oxidation-Reduction</subject><subject>Phenotype</subject><subject>Protein Denaturation</subject><subject>Protein Stability</subject><subject>Proteolysis</subject><subject>Proteome</subject><subject>Small Molecule Libraries</subject><subject>Temperature</subject><issn>1367-5931</issn><issn>1879-0402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1LwzAchoMobk7_AQ-So5fWfKxpC15k-IUDL3oOafLrzNjSmqSD_fembHoUAvmFPO9L8iB0TUlOCRV361w3vcoZoXVOWE6IOEFTWpV1RuaEnaaZizIrak4n6CKENUkEq4pzNOGk5rwS1RS9LVUDm6z1ADgqv4KIrQEXbWu1irZz2Dps_LDCxgbd7cDv8c4q3H-B6-K-txoHncLOutUlOmvVJsDVcZ-hz6fHj8VLtnx_fl08LDPNCxGzmrZGpKksVFG1dTkHXgqWzqoEXigGRW1qmI_3ShctN41ogVFTCaCi0ZTP0O2ht_fd9wAhym16G2w2ykE3BMkYSYtUJUsoO6DadyF4aGXv7Vb5vaREjhLlWo4S5ShREiaTohS6OfYPzRbMX-TXWgLuDwCkX-4seBm0BafBWA86StPZ__p_ANtMgww</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>Park, Hankum</creator><creator>Ha, Jaeyoung</creator><creator>Park, Seung Bum</creator><general>Elsevier Ltd</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></search><sort><creationdate>201906</creationdate><title>Label-free target identification in drug discovery via phenotypic screening</title><author>Park, Hankum ; Ha, Jaeyoung ; Park, Seung Bum</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-91fd635675a58f974e3762567a7e35a2e59d9e4675aac5f3db6fe21d86e16bc13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Drug Discovery</topic><topic>Electrophoresis, Gel, Two-Dimensional</topic><topic>Oxidation-Reduction</topic><topic>Phenotype</topic><topic>Protein Denaturation</topic><topic>Protein Stability</topic><topic>Proteolysis</topic><topic>Proteome</topic><topic>Small Molecule Libraries</topic><topic>Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Hankum</creatorcontrib><creatorcontrib>Ha, Jaeyoung</creatorcontrib><creatorcontrib>Park, Seung Bum</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Current opinion in chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Hankum</au><au>Ha, Jaeyoung</au><au>Park, Seung Bum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Label-free target identification in drug discovery via phenotypic screening</atitle><jtitle>Current opinion in chemical biology</jtitle><addtitle>Curr Opin Chem Biol</addtitle><date>2019-06</date><risdate>2019</risdate><volume>50</volume><spage>66</spage><epage>72</epage><pages>66-72</pages><issn>1367-5931</issn><eissn>1879-0402</eissn><abstract>[Display omitted]
Phenotypic screening has demonstrated its advantage in the discovery of first-in-class therapeutics, whereas target-based screening has showed strength for follower drugs. Owing to the unbiased nature of phenotypic screening, novel druggable proteins can be uncovered by target identification. Chemical label-free target identification methods can eliminate the functionalization step of an original bioactive compound. Herein, we summarize recent advances in the development of label-free target identification methods, which are based on changes in protein stability against proteolysis, and chemical and thermal denaturation. Owing to the increasing application of shift in thermal stability for protein analysis in live cells and tissues, we mainly focus on the cellular stability shift assay and its proteome-wide application for target identification.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30933868</pmid><doi>10.1016/j.cbpa.2019.02.006</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Drug Discovery Electrophoresis, Gel, Two-Dimensional Oxidation-Reduction Phenotype Protein Denaturation Protein Stability Proteolysis Proteome Small Molecule Libraries Temperature |
| title | Label-free target identification in drug discovery via phenotypic screening |
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