Dual Use Therapeutics for Cryptosporidiosis, Toxoplasmosis, and Neosporosis

描述（由申报单位提供）：目前急需人畜用隐孢子虫病和弓形虫病新药。隐孢子虫病导致人类和小牛消瘦性腹泻。弓形虫病是人类和家畜胎儿畸形和流产的重要原因。此外，还需要一种有效的药物用于兽医治疗新孢子病，这是牲畜流行流产的原因。该项目是继我们成功的靶向原生动物钙依赖性蛋白激酶（CDPKs）的药物开发项目之后开展的。我们现在有两种有前景的临床前候选药物，它们在隐孢子虫病、弓形虫病和新孢子虫病的小鼠模型中显示出活性，因此对兽医和人类健康都具有巨大的潜在价值。该项目的目标是对我们的新疗法在农业上重要的家畜（牛和羊）上进行疗效、药代动力学（PK）和毒性测试，以显示对动物疾病的疗效，并为人类使用的临床前药物包装收集信息。我们将把这些化合物扩大到接近一公斤的数量，在弓形虫病和新孢子虫病的绵羊模型以及隐孢子虫病的小牛模型中测试它们的功效。在这个项目的最后，目标是有一个临床前候选药物和一个或两个备用药物，以推进最终的临床前测试和IND/NADA注册，供兽医和人类使用。

DESCRIPTION (provided by applicant): New drugs are urgently needed for cryptosporidiosis and toxoplasmosis for human and domestic livestock use. Cryptosporidiosis causes wasting diarrhea in humans and calves. Toxoplasmosis is an important cause of fetal malformations and abortions in humans and domestic livestock. In addition, an effective drug is also needed for veterinary use for neosporosis, the cause of epidemic abortions in livestock. This project follows on our successful hit-to-lead drug development project, targeting protozoan Calcium Dependent Protein Kinases (CDPKs). We now have two promising pre-clinical drug candidates that show activity in mouse models of cryptosporidiosis, toxoplasmosis and neosporosis, and thus are of great potential value for both veterinary and human health. The goal of this project will be to conduct efficacy, pharmacokinetic (PK), and toxicity testing of our novel therapeutics in agriculturally-important domestic animals (cattle and sheep) to show efficacy for animal diseases and to also gather information for the preclinical drug package for human use. We will scale-up the compounds to the near kilogram quantity, test their efficacy in sheep models of toxoplasmosis and neosporosis, and in a calf model of cryptosporidiosis. In the end of this project, the goal is to have a preclinical drug candidate and one or two backups to advance to final preclinical testing and IND/NADA registration for veterinary and human use.