{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:23:49Z","timestamp":1762323829721},"reference-count":26,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The treatment of onychomycosis has improved considerably over the past several decades following the introduction of the oral antifungals terbinafine and itraconazole. However, these oral agents suffer from certain disadvantages, including drug interactions and potential liver toxicity. Thus, there is a need for new topical agents that are effective against onychomycosis. ME1111 is a novel selective inhibitor of succinate dehydrogenase (complex II) of dermatophyte species, whose small molecular weight enhances its ability to penetrate the nail plate. In this study, we determined the antifungal activity of ME1111 against dermatophyte strains, most of which are known to cause nail infections, as measured by the MIC (\n            <jats:italic>n<\/jats:italic>\n            = 400) and the minimum fungicidal concentration (MFC) (\n            <jats:italic>n<\/jats:italic>\n            = 300). Additionally, we examined the potential for resistance development in dermatophytes (\n            <jats:italic>n<\/jats:italic>\n            = 4) following repeated exposure to ME1111. Our data show that the MIC\n            <jats:sub>90<\/jats:sub>\n            of ME1111 against dermatophyte strains was 0.25 \u03bcg\/ml, which was equivalent to that of the comparators amorolfine and ciclopirox (0.25 and 0.5 \u03bcg\/ml, respectively). ME1111 was fungicidal at clinically achievable concentrations against dermatophytes, and its MFC\n            <jats:sub>90<\/jats:sub>\n            s against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trichophyton rubrum<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trichophyton mentagrophytes<\/jats:named-content>\n            were 8 \u03bcg\/ml, comparable to those of ciclopirox. Furthermore, ME1111, as well as ciclopirox, did not induce resistance in 4 dermatophytes tested. Our studies show that ME1111 possesses potent antifungal activity and suggest that it has low potential for the development of resistance in dermatophytes.\n          <\/jats:p>","DOI":"10.1128\/aac.00992-15","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T19:10:15Z","timestamp":1433963415000},"page":"5154-5158","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["<i>In Vitro<\/i>\n            Antifungal Activity of ME1111, a New Topical Agent for Onychomycosis, against Clinical Isolates of Dermatophytes"],"prefix":"10.1128","volume":"59","author":[{"given":"M.","family":"Ghannoum","sequence":"first","affiliation":[{"name":"Center for Medical Mycology, Case Western Reserve University, and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Isham","sequence":"additional","affiliation":[{"name":"Center for Medical Mycology, Case Western Reserve University, and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Long","sequence":"additional","affiliation":[{"name":"Center for Medical Mycology, Case Western Reserve University, and University Hospitals Case Medical Center, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004105"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1992.tb00005.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1997.03890450124022,10.1001\/archderm.133.9.1172"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/j.1365-2133.1995.tb00722.x","article-title":"Prevalence of dermatophyte onychomycosis in Spain: a cross-sectional study","volume":"132","author":"Sais G","year":"1995","unstructured":"Sais G, Jucgl\u00e0 A, Peyr\u00ed J. 1995. Prevalence of dermatophyte onychomycosis in Spain: a cross-sectional study. Br J Dermatol 132:758\u2013761.","journal-title":"Br J Dermatol"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.107754"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/000155502762064665"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4362.1997.00349.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2004.00968.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1998.02464.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2005.01140.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200001010-00002"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(98)70199-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008986826756"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.104794"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-0113"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00105-011-2251-5"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.149.s65.5.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(08)81262-5"},{"key":"e_1_3_2_20_2","first-page":"299","article-title":"Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality","volume":"1","author":"Elewski B","year":"2005","unstructured":"Elewski B, Tavakkol A. 2005. Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality. Ther Clin Risk Manag 1:299\u2013306.","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_3_2_21_2","article-title":"Drug therapy guidelines: antifungal agents Lamisil\u00ae (terbinafine), Sporanox\u00ae (itraconazole), Penlac\u00ae (ciclopirox), Vfend\u00ae (voriconazole)","author":"BlueShield of Northeastern New York","year":"2006","unstructured":"BlueShield of Northeastern New York. 28 November 2006. Drug therapy guidelines: antifungal agents Lamisil\u00ae (terbinafine), Sporanox\u00ae (itraconazole), Penlac\u00ae (ciclopirox), Vfend\u00ae (voriconazole). Drug P&T Newsl.","journal-title":"Drug P&T Newsl"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.1992.tb00277.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2008.01540.x"},{"key":"e_1_3_2_24_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard","author":"CLSI","year":"2008","unstructured":"CLSI. 2008. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, 2nd ed. CLSI document M38-A2. CLSI, Wayne, PA.","edition":"2"},{"key":"e_1_3_2_25_2","volume-title":"Abstr 54th Intersci Conf Antimicrob Agents Chemother","author":"Takahata S","year":"2014","unstructured":"Takahata S, Tabata Y, Takei-Masuda N, Kubota N, Maebashi K. 2014. Mechanism of action of ME1111, a new antifungal agent for the topical treatment of onychomycosis, abstr F-1585. Abstr 54th Intersci Conf Antimicrob Agents Chemother."},{"key":"e_1_3_2_26_2","volume-title":"Abstr 54th Intersci Conf Antimicrob Agents Chemother","author":"Hui X","year":"2014","unstructured":"Hui X, Maibach H. 2014. In vitro human nail plate penetration of a novel antifungal agent ME1111, abstr F-1588. Abstr 54th Intersci Conf Antimicrob Agents Chemother."},{"key":"e_1_3_2_27_2","volume-title":"Abstr 54th Intersci Confer Antimicrob Agents Chemother","author":"Tabata Y","year":"2014","unstructured":"Tabata Y, Nomoto M, Chikada T, Kubota N, Takei-Masuda N, Takahata S, Maebashi K. 2014. In vivo and in vitro nail penetration of ME1111, a novel antifungal agent for topical treatment of onychomycosis, abstr F-1589. Abstr 54th Intersci Confer Antimicrob Agents Chemother."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00992-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00992-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:55:34Z","timestamp":1645484134000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00992-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9]]},"references-count":26,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1128\/AAC.00992-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.00992-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9]]},"assertion":[{"value":"2015-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}