{"title":"治疗RyR1相关骨骼肌疾病的药物开发","authors":"Takashi Murayama , Nagomi Kurebayashi , Ryosuke Ishida , Hiroyuki Kagechika","doi":"10.1016/j.coph.2023.102356","DOIUrl":null,"url":null,"abstract":"<div><p>Type 1 ryanodine receptor (RyR1) is an intracellular Ca<sup>2+</sup><span> release channel on the sarcoplasmic reticulum<span> of skeletal muscle, and it plays a central role in excitation–contraction (E-C) coupling. Mutations in RyR1 are implicated in various muscle diseases<span> including malignant hyperthermia<span>, central core disease, and myopathies. Currently, no specific treatment exists for most of these diseases. Recently, high-throughput screening (HTS) assays have been developed for identifying potential candidates for treating RyR-related muscle diseases. Currently, two different methods, namely a FRET-based assay and an endoplasmic reticulum Ca</span></span></span></span><sup>2+</sup>-based assay, are available. These assays identified several compounds as novel RyR1 inhibitors. In addition, the development of a reconstituted platform permitted HTS assays for E-C coupling modulators. In this review, we will focus on recent progress in HTS assays and discuss future perspectives of these promising approaches.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Drug development for the treatment of RyR1-related skeletal muscle diseases\",\"authors\":\"Takashi Murayama , Nagomi Kurebayashi , Ryosuke Ishida , Hiroyuki Kagechika\",\"doi\":\"10.1016/j.coph.2023.102356\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Type 1 ryanodine receptor (RyR1) is an intracellular Ca<sup>2+</sup><span> release channel on the sarcoplasmic reticulum<span> of skeletal muscle, and it plays a central role in excitation–contraction (E-C) coupling. Mutations in RyR1 are implicated in various muscle diseases<span> including malignant hyperthermia<span>, central core disease, and myopathies. Currently, no specific treatment exists for most of these diseases. Recently, high-throughput screening (HTS) assays have been developed for identifying potential candidates for treating RyR-related muscle diseases. Currently, two different methods, namely a FRET-based assay and an endoplasmic reticulum Ca</span></span></span></span><sup>2+</sup>-based assay, are available. These assays identified several compounds as novel RyR1 inhibitors. In addition, the development of a reconstituted platform permitted HTS assays for E-C coupling modulators. In this review, we will focus on recent progress in HTS assays and discuss future perspectives of these promising approaches.</p></div>\",\"PeriodicalId\":50603,\"journal\":{\"name\":\"Current Opinion in Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2023-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Opinion in Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1471489223000097\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1471489223000097","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Drug development for the treatment of RyR1-related skeletal muscle diseases
Type 1 ryanodine receptor (RyR1) is an intracellular Ca2+ release channel on the sarcoplasmic reticulum of skeletal muscle, and it plays a central role in excitation–contraction (E-C) coupling. Mutations in RyR1 are implicated in various muscle diseases including malignant hyperthermia, central core disease, and myopathies. Currently, no specific treatment exists for most of these diseases. Recently, high-throughput screening (HTS) assays have been developed for identifying potential candidates for treating RyR-related muscle diseases. Currently, two different methods, namely a FRET-based assay and an endoplasmic reticulum Ca2+-based assay, are available. These assays identified several compounds as novel RyR1 inhibitors. In addition, the development of a reconstituted platform permitted HTS assays for E-C coupling modulators. In this review, we will focus on recent progress in HTS assays and discuss future perspectives of these promising approaches.
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Current Opinion in Pharmacology (COPHAR) publishes authoritative, comprehensive, and systematic reviews. COPHAR helps specialists keep up to date with a clear and readable synthesis on current advances in pharmacology and drug discovery. Expert authors annotate the most interesting papers from the expanding volume of information published today, saving valuable time and giving the reader insight on areas of importance.
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