A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties
Phenotypic screening is an ideal strategy for the discovery of novel bioactive molecules. Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting i...
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| Veröffentlicht in: | Frontiers in pharmacology 2020-03, Vol.11, p.237-237, Article 237 |
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| creator | El-Kadiry, Abed El-Hakim Abusarah, Jamilah Cui, Yun Emma El-Hachem, Nehme Hammond-Martel, Ian Wurtele, Hugo Thomas, Sini Ahmadi, Maryam Balood, Mohammad Talbot, Sebastien Rafei, Moutih |
| description | Phenotypic screening is an ideal strategy for the discovery of novel bioactive molecules. Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting immunomodulatory properties and discovered a sulfonyl-containing hit, we named InhiTinib. This compound inhibited interferon (IFN)-gamma production and proliferation of primary CD3(+) T cells without inducing cell death. In contrast, InhiTinib triggered apoptosis in several murine and human cancer cell lines. Besides, the compound was well tolerated by immunocompetent mice, triggered tumor regression in animals with pre-established EL4 T-cell lymphomas, and prolonged the overall survival of mice harboring advanced tumors. Altogether, our data demonstrate the anti-cancer properties of InhiTinib, which can henceforth bridge to wider-scale biochemical and clinical tests following further in-depth pharmacodynamic studies. |
| doi_str_mv | 10.3389/fphar.2020.00237 |
| format | Article |
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Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting immunomodulatory properties and discovered a sulfonyl-containing hit, we named InhiTinib. This compound inhibited interferon (IFN)-gamma production and proliferation of primary CD3(+) T cells without inducing cell death. In contrast, InhiTinib triggered apoptosis in several murine and human cancer cell lines. Besides, the compound was well tolerated by immunocompetent mice, triggered tumor regression in animals with pre-established EL4 T-cell lymphomas, and prolonged the overall survival of mice harboring advanced tumors. Altogether, our data demonstrate the anti-cancer properties of InhiTinib, which can henceforth bridge to wider-scale biochemical and clinical tests following further in-depth pharmacodynamic studies.</description><identifier>ISSN: 1663-9812</identifier><identifier>EISSN: 1663-9812</identifier><identifier>DOI: 10.3389/fphar.2020.00237</identifier><identifier>PMID: 32231565</identifier><language>eng</language><publisher>LAUSANNE: Frontiers Media Sa</publisher><subject>apoptosis ; cancer ; HTS ; Life Sciences & Biomedicine ; Pharmacology ; Pharmacology & Pharmacy ; Science & Technology ; small molecule ; sulfonyl compound ; T cells</subject><ispartof>Frontiers in pharmacology, 2020-03, Vol.11, p.237-237, Article 237</ispartof><rights>Copyright © 2020 El-Kadiry, Abusarah, Cui, El-Hachem, Hammond-Martel, Wurtele, Thomas, Ahmadi, Balood, Talbot and Rafei.</rights><rights>Copyright © 2020 El-Kadiry, Abusarah, Cui, El-Hachem, Hammond-Martel, Wurtele, Thomas, Ahmadi, Balood, Talbot and Rafei. 2020 El-Kadiry, Abusarah, Cui, El-Hachem, Hammond-Martel, Wurtele, Thomas, Ahmadi, Balood, Talbot and Rafei</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>4</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000525594700001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c462t-1a41ff4e569a247fb2b1f72c6a77a11726c2cee31e18719af4c5242ba7a949c63</citedby><cites>FETCH-LOGICAL-c462t-1a41ff4e569a247fb2b1f72c6a77a11726c2cee31e18719af4c5242ba7a949c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081885/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081885/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27929,27930,28253,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32231565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El-Kadiry, Abed El-Hakim</creatorcontrib><creatorcontrib>Abusarah, Jamilah</creatorcontrib><creatorcontrib>Cui, Yun Emma</creatorcontrib><creatorcontrib>El-Hachem, Nehme</creatorcontrib><creatorcontrib>Hammond-Martel, Ian</creatorcontrib><creatorcontrib>Wurtele, Hugo</creatorcontrib><creatorcontrib>Thomas, Sini</creatorcontrib><creatorcontrib>Ahmadi, Maryam</creatorcontrib><creatorcontrib>Balood, Mohammad</creatorcontrib><creatorcontrib>Talbot, Sebastien</creatorcontrib><creatorcontrib>Rafei, Moutih</creatorcontrib><title>A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties</title><title>Frontiers in pharmacology</title><addtitle>FRONT PHARMACOL</addtitle><addtitle>Front Pharmacol</addtitle><description>Phenotypic screening is an ideal strategy for the discovery of novel bioactive molecules. Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting immunomodulatory properties and discovered a sulfonyl-containing hit, we named InhiTinib. This compound inhibited interferon (IFN)-gamma production and proliferation of primary CD3(+) T cells without inducing cell death. In contrast, InhiTinib triggered apoptosis in several murine and human cancer cell lines. Besides, the compound was well tolerated by immunocompetent mice, triggered tumor regression in animals with pre-established EL4 T-cell lymphomas, and prolonged the overall survival of mice harboring advanced tumors. Altogether, our data demonstrate the anti-cancer properties of InhiTinib, which can henceforth bridge to wider-scale biochemical and clinical tests following further in-depth pharmacodynamic studies.</description><subject>apoptosis</subject><subject>cancer</subject><subject>HTS</subject><subject>Life Sciences & Biomedicine</subject><subject>Pharmacology</subject><subject>Pharmacology & Pharmacy</subject><subject>Science & Technology</subject><subject>small molecule</subject><subject>sulfonyl compound</subject><subject>T cells</subject><issn>1663-9812</issn><issn>1663-9812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>DOA</sourceid><recordid>eNqNkUtvEzEURkcIRKvSPSs0SyQ0Yfy2N0ghKqVSeUiFtXXHuU5cOeNgzxT675kkJWp3eGPL_r7jK52qek3aGWPavPfbNeQZbWk7a1vK1LPqlEjJGqMJff7ofFKdl3LbTosZwyR_WZ0wShkRUpxWl_P6a7rDWN-M0af-PjYfoeCyvtlAjPWXFNGNEeuLP-vQhSH0q3reD6Fx0DvM9fectpiHgOVV9cJDLHj-sJ9VPz9d_Fh8bq6_XV4t5teN45IODQFOvOcopAHKle9oR7yiToJSQIii0lGHyAgSrYgBz52gnHagwHDjJDurrg7cZYJbu81hA_neJgh2f5HyysI0kItoqTRGdl4B044LBpoIt1xy5JxyCWLH-nBgbcdug0uH_ZAhPoE-fenD2q7SnVWtJlqLCfD2AZDTrxHLYDehOIwRekxjsZRpQZUQTE_R9hB1OZWS0R-_Ia3d6bR7nXan0-51TpU3j8c7Fv7JmwL6EPiNXfLFBZykHGOTb0GFMFzt1JNFGGAIqV-ksR-m6rv_r7K_9DC8VQ</recordid><startdate>20200312</startdate><enddate>20200312</enddate><creator>El-Kadiry, Abed El-Hakim</creator><creator>Abusarah, Jamilah</creator><creator>Cui, Yun Emma</creator><creator>El-Hachem, Nehme</creator><creator>Hammond-Martel, Ian</creator><creator>Wurtele, Hugo</creator><creator>Thomas, Sini</creator><creator>Ahmadi, Maryam</creator><creator>Balood, Mohammad</creator><creator>Talbot, Sebastien</creator><creator>Rafei, Moutih</creator><general>Frontiers Media Sa</general><general>Frontiers Media S.A</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20200312</creationdate><title>A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties</title><author>El-Kadiry, Abed El-Hakim ; Abusarah, Jamilah ; Cui, Yun Emma ; El-Hachem, Nehme ; Hammond-Martel, Ian ; Wurtele, Hugo ; Thomas, Sini ; Ahmadi, Maryam ; Balood, Mohammad ; Talbot, Sebastien ; Rafei, Moutih</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-1a41ff4e569a247fb2b1f72c6a77a11726c2cee31e18719af4c5242ba7a949c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>apoptosis</topic><topic>cancer</topic><topic>HTS</topic><topic>Life Sciences & Biomedicine</topic><topic>Pharmacology</topic><topic>Pharmacology & Pharmacy</topic><topic>Science & Technology</topic><topic>small molecule</topic><topic>sulfonyl compound</topic><topic>T cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El-Kadiry, Abed El-Hakim</creatorcontrib><creatorcontrib>Abusarah, Jamilah</creatorcontrib><creatorcontrib>Cui, Yun Emma</creatorcontrib><creatorcontrib>El-Hachem, Nehme</creatorcontrib><creatorcontrib>Hammond-Martel, Ian</creatorcontrib><creatorcontrib>Wurtele, Hugo</creatorcontrib><creatorcontrib>Thomas, Sini</creatorcontrib><creatorcontrib>Ahmadi, Maryam</creatorcontrib><creatorcontrib>Balood, Mohammad</creatorcontrib><creatorcontrib>Talbot, Sebastien</creatorcontrib><creatorcontrib>Rafei, Moutih</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El-Kadiry, Abed El-Hakim</au><au>Abusarah, Jamilah</au><au>Cui, Yun Emma</au><au>El-Hachem, Nehme</au><au>Hammond-Martel, Ian</au><au>Wurtele, Hugo</au><au>Thomas, Sini</au><au>Ahmadi, Maryam</au><au>Balood, Mohammad</au><au>Talbot, Sebastien</au><au>Rafei, Moutih</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties</atitle><jtitle>Frontiers in pharmacology</jtitle><stitle>FRONT PHARMACOL</stitle><addtitle>Front Pharmacol</addtitle><date>2020-03-12</date><risdate>2020</risdate><volume>11</volume><spage>237</spage><epage>237</epage><pages>237-237</pages><artnum>237</artnum><issn>1663-9812</issn><eissn>1663-9812</eissn><abstract>Phenotypic screening is an ideal strategy for the discovery of novel bioactive molecules. Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting immunomodulatory properties and discovered a sulfonyl-containing hit, we named InhiTinib. This compound inhibited interferon (IFN)-gamma production and proliferation of primary CD3(+) T cells without inducing cell death. In contrast, InhiTinib triggered apoptosis in several murine and human cancer cell lines. Besides, the compound was well tolerated by immunocompetent mice, triggered tumor regression in animals with pre-established EL4 T-cell lymphomas, and prolonged the overall survival of mice harboring advanced tumors. 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| subjects | apoptosis cancer HTS Life Sciences & Biomedicine Pharmacology Pharmacology & Pharmacy Science & Technology small molecule sulfonyl compound T cells |
| title | A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties |
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