Development of High-Throughput Screening Assays for Inhibitors of ETS Transcription Factors
ETS transcription factors from the ERG and ETV1/4/5 subfamilies are overexpressed in the majority of prostate cancer patients and contribute to disease progression. Here, we have developed two in vitro assays for the interaction of ETS transcription factors with DNA that are amenable to high-through...
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| Veröffentlicht in: | SLAS discovery 2019-01, Vol.24 (1), p.77-85 |
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| creator | Currie, Simon L. Warner, Steven L. Vankayalapati, Hariprasad Liu, Xiaohui Sharma, Sunil Bearss, David J. Graves, Barbara J. |
| description | ETS transcription factors from the ERG and ETV1/4/5 subfamilies are overexpressed in the majority of prostate cancer patients and contribute to disease progression. Here, we have developed two in vitro assays for the interaction of ETS transcription factors with DNA that are amenable to high-throughput screening. Using ETS1 as a model, we applied these assays to screen 110 compounds derived from a high-throughput virtual screen. We found that the use of lower-affinity DNA binding sequences, similar to those that ERG and ETV1 bind to in prostate cells, allowed for higher inhibition from many of these test compounds. Further pilot experiments demonstrated that the in vitro assays are robust for ERG, ETV1, and ETV5, three of the ETS transcription factors that are overexpressed in prostate cancer. |
| doi_str_mv | 10.1177/2472555218798571 |
| format | Article |
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Here, we have developed two in vitro assays for the interaction of ETS transcription factors with DNA that are amenable to high-throughput screening. Using ETS1 as a model, we applied these assays to screen 110 compounds derived from a high-throughput virtual screen. We found that the use of lower-affinity DNA binding sequences, similar to those that ERG and ETV1 bind to in prostate cells, allowed for higher inhibition from many of these test compounds. Further pilot experiments demonstrated that the in vitro assays are robust for ERG, ETV1, and ETV5, three of the ETS transcription factors that are overexpressed in prostate cancer.</description><subject>Cell Line, Tumor</subject><subject>DNA-Binding Proteins - genetics</subject><subject>High-Throughput Screening Assays - methods</subject><subject>Humans</subject><subject>Male</subject><subject>Prostate - metabolism</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Proto-Oncogene Proteins c-ets - genetics</subject><subject>Transcriptional Regulator ERG - genetics</subject><issn>2472-5552</issn><issn>2472-5560</issn><issn>2472-5560</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFPwyAUxonRuGXu7sn06KUKFEp7MTFzc0tMPGyePBBKaYvpoEJr4n8vy-aiJoYDhPd9P97jA-ASwRuEGLvFhGFKKUYZyzPK0AkY765iSlN4ejxTPAJT798ghIilSVjnYJRADAlNyBi8PqgP1dpuq0wf2Spa6rqJN42zQ910Qx-tpVPKaFNH996LTx9V1kUr0-hC99b5nWW-WUcbJ4yXTne9tiZaCLkrXoCzSrReTQ_7BLws5pvZMn56flzN7p9iSRLSxzmWihKJIGYSolQWisiyIFkqE4JVmUJRwSIrchrGLQlLK0XyjAnECCIlzLNkAu723G4otqqUYRQnWt45vRXuk1uh-e-K0Q2v7QcPhJTkLACuDwBn3wfle77VXqq2FUbZwXMcessxSlgepHAvlc5671R1fAZBvouF_40lWK5-tnc0fIcQBPFe4EWt-JsdnAnf9T_wCzuylaY</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Currie, Simon L.</creator><creator>Warner, Steven L.</creator><creator>Vankayalapati, Hariprasad</creator><creator>Liu, Xiaohui</creator><creator>Sharma, Sunil</creator><creator>Bearss, David J.</creator><creator>Graves, Barbara J.</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>5PM</scope><orcidid>https://orcid.org/0000-0001-5083-1484</orcidid></search><sort><creationdate>20190101</creationdate><title>Development of High-Throughput Screening Assays for Inhibitors of ETS Transcription Factors</title><author>Currie, Simon L. ; Warner, Steven L. ; Vankayalapati, Hariprasad ; Liu, Xiaohui ; Sharma, Sunil ; Bearss, David J. ; Graves, Barbara J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-92ce54c1027c016cbe4cdb486c342ed60af0b8b95725d476fe4987a17414d0983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Cell Line, Tumor</topic><topic>DNA-Binding Proteins - genetics</topic><topic>High-Throughput Screening Assays - methods</topic><topic>Humans</topic><topic>Male</topic><topic>Prostate - metabolism</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Proto-Oncogene Proteins c-ets - genetics</topic><topic>Transcriptional Regulator ERG - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Currie, Simon L.</creatorcontrib><creatorcontrib>Warner, Steven L.</creatorcontrib><creatorcontrib>Vankayalapati, Hariprasad</creatorcontrib><creatorcontrib>Liu, Xiaohui</creatorcontrib><creatorcontrib>Sharma, Sunil</creatorcontrib><creatorcontrib>Bearss, David J.</creatorcontrib><creatorcontrib>Graves, Barbara J.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>SLAS discovery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Currie, Simon L.</au><au>Warner, Steven L.</au><au>Vankayalapati, Hariprasad</au><au>Liu, Xiaohui</au><au>Sharma, Sunil</au><au>Bearss, David J.</au><au>Graves, Barbara J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of High-Throughput Screening Assays for Inhibitors of ETS Transcription Factors</atitle><jtitle>SLAS discovery</jtitle><addtitle>J Biomol Screen</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>24</volume><issue>1</issue><spage>77</spage><epage>85</epage><pages>77-85</pages><issn>2472-5552</issn><issn>2472-5560</issn><eissn>2472-5560</eissn><abstract>ETS transcription factors from the ERG and ETV1/4/5 subfamilies are overexpressed in the majority of prostate cancer patients and contribute to disease progression. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Cell Line, Tumor DNA-Binding Proteins - genetics High-Throughput Screening Assays - methods Humans Male Prostate - metabolism Prostatic Neoplasms - genetics Proto-Oncogene Proteins c-ets - genetics Transcriptional Regulator ERG - genetics |
| title | Development of High-Throughput Screening Assays for Inhibitors of ETS Transcription Factors |
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