The FDA-approved drugs ticlopidine, sertaconazole, and dexlansoprazole can cause morphological changes in C. elegans
Urgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our understanding of their mechanism of action and enable better therapies. We screened a library of 1443 Food and Drug Administration (FDA)-ap...
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Veröffentlicht in: | Chemosphere (Oxford) 2020-12, Vol.261, p.127756-127756, Article 127756 |
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creator | Galford, Kyle F. Jose, Antony M. |
description | Urgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our understanding of their mechanism of action and enable better therapies. We screened a library of 1443 Food and Drug Administration (FDA)-approved drugs using a simple assay in the nematode C. elegans and found three compounds that caused morphological changes. While the anticoagulant ticlopidine and the antifungal sertaconazole caused both accumulations that resulted in distinct distortions of pharyngeal anatomy and lethality upon acute exposure, the proton-pump inhibitor dexlansoprazole caused molting defects and required exposure during larval development. Such easily detectable defects in a powerful genetic model system advocate the continued exploration of current medicines using a variety of model organisms to better understand drugs already prescribed to millions of patients.
[Display omitted]
•The nematode C. elegans was modified to make a drug-sensitive strain.•Three FDA-approved drugs found using the strain can alter wild-type C. elegans.•Ticlopidine and Sertaconazole cause accumulations & lethality upon acute exposure.•Dexlansoprazole causes defects in molting upon exposure during larval development. |
doi_str_mv | 10.1016/j.chemosphere.2020.127756 |
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[Display omitted]
•The nematode C. elegans was modified to make a drug-sensitive strain.•Three FDA-approved drugs found using the strain can alter wild-type C. elegans.•Ticlopidine and Sertaconazole cause accumulations & lethality upon acute exposure.•Dexlansoprazole causes defects in molting upon exposure during larval development.</description><identifier>ISSN: 0045-6535</identifier><identifier>EISSN: 1879-1298</identifier><identifier>DOI: 10.1016/j.chemosphere.2020.127756</identifier><identifier>PMID: 32731027</identifier><language>eng</language><publisher>Elsevier Ltd</publisher><subject>Epigenetic sensor ; Genetic screen ; Marginal cells ; Molting ; Toxicology</subject><ispartof>Chemosphere (Oxford), 2020-12, Vol.261, p.127756-127756, Article 127756</ispartof><rights>2020 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-8f4b2b70caf750c81522cca6eac02dfa96e0ae0749322b5afed379c7ec3ff5243</citedby><cites>FETCH-LOGICAL-c460t-8f4b2b70caf750c81522cca6eac02dfa96e0ae0749322b5afed379c7ec3ff5243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.chemosphere.2020.127756$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids></links><search><creatorcontrib>Galford, Kyle F.</creatorcontrib><creatorcontrib>Jose, Antony M.</creatorcontrib><title>The FDA-approved drugs ticlopidine, sertaconazole, and dexlansoprazole can cause morphological changes in C. elegans</title><title>Chemosphere (Oxford)</title><description>Urgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our understanding of their mechanism of action and enable better therapies. We screened a library of 1443 Food and Drug Administration (FDA)-approved drugs using a simple assay in the nematode C. elegans and found three compounds that caused morphological changes. While the anticoagulant ticlopidine and the antifungal sertaconazole caused both accumulations that resulted in distinct distortions of pharyngeal anatomy and lethality upon acute exposure, the proton-pump inhibitor dexlansoprazole caused molting defects and required exposure during larval development. Such easily detectable defects in a powerful genetic model system advocate the continued exploration of current medicines using a variety of model organisms to better understand drugs already prescribed to millions of patients.
[Display omitted]
•The nematode C. elegans was modified to make a drug-sensitive strain.•Three FDA-approved drugs found using the strain can alter wild-type C. elegans.•Ticlopidine and Sertaconazole cause accumulations & lethality upon acute exposure.•Dexlansoprazole causes defects in molting upon exposure during larval development.</description><subject>Epigenetic sensor</subject><subject>Genetic screen</subject><subject>Marginal cells</subject><subject>Molting</subject><subject>Toxicology</subject><issn>0045-6535</issn><issn>1879-1298</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqNkcFq3DAQhkVIabbbvoN6rzeybEnrSyFsmrYQyCU9i9nx2NbilYzkXZI-TZ6lT1alG0p7y2EY5p_5fhh-xj6WYlWKUl_uVjjQPqRpoEgrKWTWpTFKn7FFuTZNUcpmfc4WQtSq0KpSF-xdSjshMqyat-yikqYqhTQLdrgfiN9cXxUwTTEcqeVtPPSJzw7HMLnWefrEE8UZMHj4GcY8gs9X9DCCT2GKf0SO4HMdEvF9iNMQxtA7hJHjAL6nxJ3nm9WvJxqpz9h79qaDMdGHl75kP26-3G--Fbd3X79vrm4LrLWYi3VXb-XWCITOKIHrUkmJCJoAhWw7aDQJIGHqppJyq6CjtjINGsKq65SsqyX7fPKdDts9tUh-jjDaKbo9xEcbwNn_N94Ntg9Ha7TQOtsuWXMywBhSitT9ZUthn7OwO_tPFvY5C3vKIrObE0v5w6OjaBM68kiti4SzbYN7hctvCgKcRQ</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Galford, Kyle F.</creator><creator>Jose, Antony M.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20201201</creationdate><title>The FDA-approved drugs ticlopidine, sertaconazole, and dexlansoprazole can cause morphological changes in C. elegans</title><author>Galford, Kyle F. ; Jose, Antony M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-8f4b2b70caf750c81522cca6eac02dfa96e0ae0749322b5afed379c7ec3ff5243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Epigenetic sensor</topic><topic>Genetic screen</topic><topic>Marginal cells</topic><topic>Molting</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Galford, Kyle F.</creatorcontrib><creatorcontrib>Jose, Antony M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemosphere (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Galford, Kyle F.</au><au>Jose, Antony M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The FDA-approved drugs ticlopidine, sertaconazole, and dexlansoprazole can cause morphological changes in C. elegans</atitle><jtitle>Chemosphere (Oxford)</jtitle><date>2020-12-01</date><risdate>2020</risdate><volume>261</volume><spage>127756</spage><epage>127756</epage><pages>127756-127756</pages><artnum>127756</artnum><issn>0045-6535</issn><eissn>1879-1298</eissn><abstract>Urgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our understanding of their mechanism of action and enable better therapies. We screened a library of 1443 Food and Drug Administration (FDA)-approved drugs using a simple assay in the nematode C. elegans and found three compounds that caused morphological changes. While the anticoagulant ticlopidine and the antifungal sertaconazole caused both accumulations that resulted in distinct distortions of pharyngeal anatomy and lethality upon acute exposure, the proton-pump inhibitor dexlansoprazole caused molting defects and required exposure during larval development. Such easily detectable defects in a powerful genetic model system advocate the continued exploration of current medicines using a variety of model organisms to better understand drugs already prescribed to millions of patients.
[Display omitted]
•The nematode C. elegans was modified to make a drug-sensitive strain.•Three FDA-approved drugs found using the strain can alter wild-type C. elegans.•Ticlopidine and Sertaconazole cause accumulations & lethality upon acute exposure.•Dexlansoprazole causes defects in molting upon exposure during larval development.</abstract><pub>Elsevier Ltd</pub><pmid>32731027</pmid><doi>10.1016/j.chemosphere.2020.127756</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Epigenetic sensor Genetic screen Marginal cells Molting Toxicology |
title | The FDA-approved drugs ticlopidine, sertaconazole, and dexlansoprazole can cause morphological changes in C. elegans |
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