{"title":"恰加斯病药物发现的新时代?","authors":"Martine Keenan, Jason H Chaplin","doi":"10.1016/bs.pmch.2014.12.001","DOIUrl":null,"url":null,"abstract":"<p><p>Recent clinical trials investigating treatment of chronic indeterminate Chagas disease with two re-purposed azole anti-fungal drugs, posaconazole and ravuconazole, revealed their inferiority to the current standard-of-care benznidazole and highlighted the inadequacy of the existing pre-clinical testing paradigm for this disease. A very limited number of controlled clinical trials for Chagas disease have been conducted to date. The selection of these compounds for clinical evaluation relied heavily on pre-clinical data obtained from in vitro screens and animal studies. This chapter reviews the evolution of CYP51 as a target for Trypanosoma cruzi growth inhibition and also explores the impact of clinical trial data on contemporary Chagas disease drug discovery. Advances in pre-clinical profiling assays, the current compound landscape and progress towards the identification of new drug targets to re-invigorate research are reviewed. </p>","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.pmch.2014.12.001","citationCount":"37","resultStr":"{\"title\":\"A new era for chagas disease drug discovery?\",\"authors\":\"Martine Keenan, Jason H Chaplin\",\"doi\":\"10.1016/bs.pmch.2014.12.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Recent clinical trials investigating treatment of chronic indeterminate Chagas disease with two re-purposed azole anti-fungal drugs, posaconazole and ravuconazole, revealed their inferiority to the current standard-of-care benznidazole and highlighted the inadequacy of the existing pre-clinical testing paradigm for this disease. A very limited number of controlled clinical trials for Chagas disease have been conducted to date. The selection of these compounds for clinical evaluation relied heavily on pre-clinical data obtained from in vitro screens and animal studies. This chapter reviews the evolution of CYP51 as a target for Trypanosoma cruzi growth inhibition and also explores the impact of clinical trial data on contemporary Chagas disease drug discovery. Advances in pre-clinical profiling assays, the current compound landscape and progress towards the identification of new drug targets to re-invigorate research are reviewed. </p>\",\"PeriodicalId\":20755,\"journal\":{\"name\":\"Progress in medicinal chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2015-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/bs.pmch.2014.12.001\",\"citationCount\":\"37\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Progress in medicinal chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/bs.pmch.2014.12.001\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2015/1/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in medicinal chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/bs.pmch.2014.12.001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2015/1/17 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
Recent clinical trials investigating treatment of chronic indeterminate Chagas disease with two re-purposed azole anti-fungal drugs, posaconazole and ravuconazole, revealed their inferiority to the current standard-of-care benznidazole and highlighted the inadequacy of the existing pre-clinical testing paradigm for this disease. A very limited number of controlled clinical trials for Chagas disease have been conducted to date. The selection of these compounds for clinical evaluation relied heavily on pre-clinical data obtained from in vitro screens and animal studies. This chapter reviews the evolution of CYP51 as a target for Trypanosoma cruzi growth inhibition and also explores the impact of clinical trial data on contemporary Chagas disease drug discovery. Advances in pre-clinical profiling assays, the current compound landscape and progress towards the identification of new drug targets to re-invigorate research are reviewed.
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This series has a long established reputation for excellent coverage of almost every facet of Medicinal Chemistry and is one of the most respected and instructive sources of information on the subject. The latest volume certifies to the continuing success of a unique series reflecting current progress in a broadly developing field of science.
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