Preclinical development of novel small molecule malaria drugs that overcome drug

克服药物障碍的新型小分子疟疾药物的临床前开发

• 批准号: 8317596
• 负责人: DAVID H PEYTON
• 金额: $ 30万
• 依托单位: DESIGNMEDIX, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8317596
• 关键词: Abbreviations; Acute; Adverse effects; Antimalarials; Back; Carrier Proteins; Child; Chloroquine; Chloroquine resistance; Clinical Research; Clinical Trials; Combined Modality Therapy; Development; Disease; Dose; Drug Design; Drug Kinetics; Drug resistance; Ethers; Evaluation; Funding; Future; Gene Proteins; Goals; Grant; Health; Health Sciences; Human; In Vitro; Inhibitory Concentration 50; Institutes; Intravenous; Investigational Drugs; Lead; Lethal Dose 50; Link; Malaria; Monkeys; Multi-Drug Resistance; Mus; National Institute of Allergy and Infectious Disease; Neuraxis; Oral cavity; Oregon; Parasites; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Plasmodium falciparum; Preclinical Drug Development; Preclinical Testing; Predisposition; Pregnant Women; Pump; Rattus; Research Contracts; Research Design; Resistance; Small Business Technology Transfer Research; Structure; Structure-Activity Relationship; Technology; Therapeutic Index; Toxic effect; Translational Research; Tropical Disease; United States Food and Drug Administration; Universities; Vacuole; Work; chemosensitizing agent; chemotherapy; cost; cytotoxicity; design; drug candidate; drug development; fitness; flexibility; in vivo; innovation; killings; meetings; mouse model; novel; pre-clinical; preclinical evaluation; preclinical study; programs; research and development; resistant strain; response; single molecule; small molecule

DESCRIPTION (provided by applicant): The worldwide health problem created by malaria has been made more difficult by the spread of drug- resistant parasites. This project initiates preclinical development of one or more candidate(s) from an innovative new class of potent antimalarials designed to overcome drug resistance. We have developed an orally available and inexpensive class of novel drugs that act against both chloroquine-resistant and chloroquine-sensitive malaria. A small set of carefully-selected candidates will be advanced through preclinical testing, leading to the selection of a single drug for a pre-Investigational New Drug meeting with the Food and Drug Administration. With guidance from the Food and Drug Administration, pharmacokinetics, pharmacodynamics, pharmacology, and toxicity evaluations will be performed in both rats and monkeys in phase II of this work. The overall goal will be completion of preclinical studies leading to approval of the Investigative New Drug (IND) application for a drug to be used in a Phase-1 human clinical trial.

描述（由申请人提供）：疟疾造成的全球性健康问题由于抗药性寄生虫的传播而变得更加困难。该项目启动了一种或多种候选药物的临床前开发，这些候选药物来自旨在克服耐药性的新型强效抗疟药。我们已经开发了一种口服的廉价新药，可以对抗氯喹耐药性和氯喹敏感性疟疾。一小部分经过精心挑选的候选药物将通过临床前测试进行推进，最终选择一种药物用于与美国食品药品监督管理局（FDA）举行的新药研究前会议。在美国食品药品监督管理局的指导下，将在本研究的第II阶段对大鼠和猴进行药代动力学、药效学、药理学和毒性评价。总体目标将是完成临床前研究，从而批准用于1期人体临床试验的药物的研究性新药（IND）申请。