NOVEL MAGAININ DRUGS FOR PSEUDOMEMBRANOUS COLITIS

治疗假膜性结肠炎的新型药物

• 批准号: 3507429
• 负责人: W LEE MALOY
• 金额: $ 25万
• 依托单位: GENAERA CORPORATION
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3507429
• 关键词: Clostridium; antibacterial agents; antibody; atrial natriuretic peptide; chemical stability; colitis; cytotoxicity; disease /disorder model; drug adverse effect; drug design /synthesis /production; drug interactions; gastrointestinal disorder chemotherapy; gastrointestinal pharmacology; hamsters; membrane channels; oral administration; peptide chemical synthesis; pharmacokinetics; proteolysis; synthetic peptide; toxicant screening

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.

描述：（改编自申请人的摘要）。 长期目标 目标是： (1) 开发和销售新型 Magainin 肽药物来治疗 C. 艰难梭菌相关的伪膜性结肠炎，目前的治疗方法是 不满意； (2) 提高知识和治疗潜力 离子通道形成肽药物。 方法包括体外结构 活性研究设计具有最大窄谱的马格宁药物 对抗艰难梭菌的活性，可抵抗胃肠道蛋白水解 酶，并且不会诱导耐药性的产生。 最活跃的 通过结构活性关系研究开发的化合物也将 测试了与针对艰难梭菌的主要药物的协同作用。 最 活性化合物和协同组合将在体内进行测试 仓鼠模型。 那些具有最大体内功效的药物将被配制用于 口头交付；稳定性、病理学和毒理学研究将 执行。该项目可能会产生重要的胃肠道药物 提高了对艰难梭菌的效力和巨大的市场潜力。 它 还将推进肽抗生素和宿主防御领域的发展 治疗。