NOVEL MAGAININ DRUGS FOR PSEUDOMEMBRANOUS COLITIS

描述：(改编自申请人的摘要)。长期目标 主要目标是：(1)开发和销售治疗C。 艰难梭菌相关性伪膜性结肠炎，目前的治疗方法是 不尽如人意；及(2)提高对 离子通道形成肽类药物。方法学包括体外结构 设计最大窄谱Mainin药物的活性研究 对艰难梭菌的活性，抵抗胃肠道蛋白水解酶 酶，并且不会导致抗药性的发展。最活跃的 通过构效关系研究开发的化合物也将 测试了与对抗艰难梭菌的主要药物的协同作用。最多的 活性化合物和增效组合将在体内进行测试 仓鼠模型。体内疗效最好的药物将用于 口服给药；稳定性、病理学和毒理学研究 已执行。该项目可能会生产出重要的胃肠道药物 提高了对艰难梭菌的效力和极大的市场潜力。它 还将促进多肽抗生素和宿主防御领域的发展 心理治疗。

DESCRIPTION: (Adapted from the Applicant's Abstract). Long-term objectives are to: (1) develop and market novel magainin peptide drugs to treat C. difficile-related pseudomembranous colitis, for which current therapy is unsatisfactory; and (2) advance the knowledge and therapeutic potential of ion channel-forming peptide drugs. Methodology includes in vitro structure activity studies to design magainin drugs with maximum narrow spectrum activity against C. difficile, which resist gastrointestinal proteolytic enzymes, and do not induce resistance development. The most active compounds developed by structure activity relationship studies will also be tested for synergy with the leading drugs against C. difficile. The most active compounds and synergistic combinations will be tested in the in vivo hamster model. Those with greatest in vivo efficacy will be formulated for oral delivery; and stability, pathology, and toxicology studies will be performed. This project may yield important gastrointestinal drugs with improved potency against C. difficile and excellent market potential. It will also advance the fields of peptide antibiotics and host defense therapy.