Preclinical development of novel small molecule malaria drugs that overcome drug

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。 公共卫生相关性：疟疾是一种每年感染约5亿人的疾病，造成近100万人死亡，其中大多数是儿童或孕妇。疟疾的影响正在增加，部分原因是导致疟疾的寄生虫已经进化成对目前治疗这种疾病的最佳药物具有抗药性的菌株。该项目涉及旨在规避这种耐药性的新药的临床前评估，为批准人体临床试验铺平道路。这些候选药物在早期研究中显示出有希望的结果，并且被设计为对所有目标群体（包括孕妇和儿童）都是廉价和安全的。

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. PUBLIC HEALTH RELEVANCE: Malaria is a disease that infects about half a billion people annually, and kills nearly one million, most of whom are children or pregnant women. The impact of malaria is increasing, partly because the parasite that causes malaria has evolved into strains that are resistant to the best current drugs for treating the disease. This project involves preclinical evaluation of novel drugs designed to circumvent this resistance, paving the way toward approval for human clinical trials. The drug candidates show promising results in early studies, and are designed to be inexpensive as well as safe for all target groups, including pregnant women and children.