{"title":"抗疟药物发现的创新:新的靶点和线索。","authors":"Neha Jeena, Lata Panicker, Inshad Ali Khan","doi":"10.2174/0113894501380738250414111540","DOIUrl":null,"url":null,"abstract":"<p><p>Malaria control is severely hindered by a lack of effective treatment options and the rise of drug-resistant strains of the parasite. Despite the absence of a reliable vaccine, the thera-peutic application of antimalarial drugs remains the primary strategy for controlling and prevent-ing malaria. However, most existing antimalarial drugs target the blood stage of the parasite's lifecycle and may not effectively eliminate liver-stage parasites, limiting their efficacy in com-plete parasite clearance. The urgent need for novel antimalarial drugs with innovative mecha-nisms of action is critical to preventing a major public health crisis. Developing new antimalarial drugs involves both optimizing existing compounds and designing novel molecules that target unique biological pathways in Plasmodium. This review explores promising drug targets, includ-ing heme detoxification, food vacuole function, mitochondria, protein kinases, apicoplast path-ways, nucleic acid biosynthesis, fatty acid metabolism, the electron transport chain (ETC), and P-Type ATPases. Lead candidates targeting these mechanisms are discussed, highlighting their po-tential as next-generation antimalarial agents. Additionally, we provide updates on clinically vali-dated targets and the progress of antimalarial drug candidates in different stages of clinical devel-opment. Emerging therapeutic strategies focusing on malarial transporters, protein interaction networks, and substrate repertoires offer new avenues for drug discovery. A deeper understanding of these pathways can enhance drug efficacy, mitigate resistance, and support the development of long-lasting antimalarial therapies. This review aims to provide insights into the current landscape of antimalarial drug development and future directions for combating malaria.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Innovations in Antimalarial Drug Discovery: New Targets and Leads.\",\"authors\":\"Neha Jeena, Lata Panicker, Inshad Ali Khan\",\"doi\":\"10.2174/0113894501380738250414111540\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Malaria control is severely hindered by a lack of effective treatment options and the rise of drug-resistant strains of the parasite. Despite the absence of a reliable vaccine, the thera-peutic application of antimalarial drugs remains the primary strategy for controlling and prevent-ing malaria. However, most existing antimalarial drugs target the blood stage of the parasite's lifecycle and may not effectively eliminate liver-stage parasites, limiting their efficacy in com-plete parasite clearance. The urgent need for novel antimalarial drugs with innovative mecha-nisms of action is critical to preventing a major public health crisis. Developing new antimalarial drugs involves both optimizing existing compounds and designing novel molecules that target unique biological pathways in Plasmodium. This review explores promising drug targets, includ-ing heme detoxification, food vacuole function, mitochondria, protein kinases, apicoplast path-ways, nucleic acid biosynthesis, fatty acid metabolism, the electron transport chain (ETC), and P-Type ATPases. Lead candidates targeting these mechanisms are discussed, highlighting their po-tential as next-generation antimalarial agents. Additionally, we provide updates on clinically vali-dated targets and the progress of antimalarial drug candidates in different stages of clinical devel-opment. Emerging therapeutic strategies focusing on malarial transporters, protein interaction networks, and substrate repertoires offer new avenues for drug discovery. A deeper understanding of these pathways can enhance drug efficacy, mitigate resistance, and support the development of long-lasting antimalarial therapies. This review aims to provide insights into the current landscape of antimalarial drug development and future directions for combating malaria.</p>\",\"PeriodicalId\":10805,\"journal\":{\"name\":\"Current drug targets\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-04-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current drug targets\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0113894501380738250414111540\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113894501380738250414111540","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Innovations in Antimalarial Drug Discovery: New Targets and Leads.
Malaria control is severely hindered by a lack of effective treatment options and the rise of drug-resistant strains of the parasite. Despite the absence of a reliable vaccine, the thera-peutic application of antimalarial drugs remains the primary strategy for controlling and prevent-ing malaria. However, most existing antimalarial drugs target the blood stage of the parasite's lifecycle and may not effectively eliminate liver-stage parasites, limiting their efficacy in com-plete parasite clearance. The urgent need for novel antimalarial drugs with innovative mecha-nisms of action is critical to preventing a major public health crisis. Developing new antimalarial drugs involves both optimizing existing compounds and designing novel molecules that target unique biological pathways in Plasmodium. This review explores promising drug targets, includ-ing heme detoxification, food vacuole function, mitochondria, protein kinases, apicoplast path-ways, nucleic acid biosynthesis, fatty acid metabolism, the electron transport chain (ETC), and P-Type ATPases. Lead candidates targeting these mechanisms are discussed, highlighting their po-tential as next-generation antimalarial agents. Additionally, we provide updates on clinically vali-dated targets and the progress of antimalarial drug candidates in different stages of clinical devel-opment. Emerging therapeutic strategies focusing on malarial transporters, protein interaction networks, and substrate repertoires offer new avenues for drug discovery. A deeper understanding of these pathways can enhance drug efficacy, mitigate resistance, and support the development of long-lasting antimalarial therapies. This review aims to provide insights into the current landscape of antimalarial drug development and future directions for combating malaria.
期刊介绍:
Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes.
Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.