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AP 4. Drug Screening and Pharmacology

AP 4. 药物筛选和药理学

基本信息

批准号：
8918047
负责人：
Eric W Schmidt
金额：
$ 15.23万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8918047
关键词：
Anti-Bacterial Agents Antibiotics Antineoplastic Agents Antiparasitic Agents Bacterial Infections Biological Assay Biological Factors Cells Characteristics Chemistry Communicable Diseases Data Development Disadvantaged Disease Drops Drug resistance Ethics Glioblastoma Goals Health Human Infection Institution Ion Channel Laws Lead Legal Letters Libraries Ligands Location Malignant Neoplasms Malignant neoplasm of pancreas Mammalian Cell Methodology Methods Microbiology Molecular Target National Institute of Allergy and Infectious Disease National Institute of Mental Health Neurologic Neurons Output Parasites Parasitic Diseases Pharmaceutical Preparations Pharmacologic Substance Pharmacology Phenotype Philippines Physiological Preclinical Drug Evaluation Proteins Psychotropic Drugs Research Resistance Resources Running Screening for cancer Source Symbiosis Technology Transfer Testing Therapeutic Therapeutic Agents Time Toxoplasma Transcription Factor AP-2 Alpha Translating United States National Institutes of Health Utah Work base cancer pharmacology cell type cost cytotoxicity drug discovery effective therapy high throughput screening human disease improved inhibitor/antagonist innovation malignant neurologic neoplasms neglect novel novel strategies novel therapeutics pain receptor pathogen phase change programs receptor screening serotonin receptor

项目摘要

Summary: AP4 This associate program of PMS-ICBG will test natural products identified in AP3 for their pharmaceutical potential in treating several important diseases. We have selected our disease targets by considering:1) unmet needs in human health; 2) health needs in the Philippines; 3) assays that have a strong tie to our eco-rationale and symbiosis studies in AP2; 4) that provide a mix of innovative and conservative approaches to drug discovery. Our assays target conditions that involve neuronal receptors, ion channels, and other proteins; pancreatic cancer; glioblastoma; pandrug-resistant "ESKAPE" infections; and apicomplexan parasite infections, with a focus on Crytosporidium and Toxoplasma. Further, we have formed interactions with appropriate entities that have further assays available and that are well suited to help us translate discoveries into products that will have a positive impact on human health. A particularly innovative focus of this AP is our use of the recently invented "constellation pharmacology" method, which provides a method for high-content screening against naturally differentiated mammalian cell types. Preliminary data show that this method is very promising in finding ligands for very challenging targets, and here we will take that further by screening natural products. This and other innovative methods proposed are reinforced with time-tested approaches to drug discovery to provide a relatively comprehensive screening of our library. Finally, we have developed strategies to validate hits and to determine their translational potential early on in studies. Promising candidates will be further investigated as part of this program. To achieve these goals, we plan to: 1) Screen priority extracts from AP3; 2) Employ constellation screening for neurological and cancer drug discovery; 3) Employ novel assays for antibiotic discovery; 4) Employ novel assays against parasites; 5) Identify molecular targets and further develop compounds.

摘要:AP4