Kinase Targeted Antimalarial Agents

激酶靶向抗疟药

• 批准号: 9918203
• 负责人: REENA ZUTSHI
• 金额: $ 95.77万
• 依托单位: LUCEOME BIOTECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-16 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9918203
• 关键词: Affect; Affinity; Anopheles Genus; Antimalarials; Artemisinins; Binding; Biological Assay; Biology; CSNK1A1 gene; Cessation of life; Chemicals; Clinical; Collection; Combined Modality Therapy; Communities; Country; Culicidae; Data; Development; Disease; Drug Targeting; Drug resistance; Erythrocytes; Goals; Health; Human; Human Bites; Incidence; Infection; Investments; Lead; Libraries; Life Cycle Stages; Luciferases; Malaria; Maps; Medicine; Morbidity - disease rate; Parasites; Pathology; Pharmaceutical Preparations; Phase; Phenotype; Phosphotransferases; Plasmodium; Plasmodium falciparum; Plasmodium falciparum genome; Plasmodium vivax; Private Sector; Protein Kinase; Public Sector; Publishing; Reporting; Research; Resistance; Series; Technology; Trees; asexual; base; candidate selection; clinical candidate; combat; design; disorder control; drug development; genome sequencing; improved; in vivo; inhibitor/antagonist; kinase inhibitor; knockout gene; member; mortality; next generation; novel; novel therapeutics; open source; phosphoproteomics; programs; protein kinase inhibitor; scaffold; screening; small molecule; tool

Project Summary The genome of Plasmodium falciparum, the species responsible for most mortality in malaria, is predicted to encode 86-99 protein kinases. Of these, 36 kinases are expressed in the asexual stage of the parasite’s life-cycle, which is responsible for the pathology associated with the disease. Using our proprietary KinaseSeeker technology, we have recently developed assays against 11 Plasmodium falciparum kinases, which are expressed in the asexual stage. Screening a small-molecule kinase inhibitor library has revealed several chemically tractable chemotypes that bind P. falciparum kinases with sub-micromolar affinity. In this application, using a target-based approach, we aim to utilize the chemotypes identified from our screening data, as starting points for development of potent and selective antimalarial agents. In addition, we will use the already commercialized P. falciparum kinase assays, to identify targets for potential kinase inhibitors that have been shown to be active in phenotypic screens against the parasite. The different series of compounds will then be further optimized for potency and selectivity to deliver leads for new antimalarials and improve human health.

项目总结