NRTS AS THERAPEUTICS FOR INFLAMMATORY BOWEL DISEASE

描述(改编自申请)：治疗和预防 炎症性肠病(IBD)的衰弱症状是一种 未得到满足的医疗需求。这项建议是为了支持第二阶段的研究，以进一步 开发半人马的领先IBD候选人。在第一阶段赠款期间 对先导候选化合物CPI-1189的化学结构进行了有序优化 改善其在活体大鼠IBD模型中的疗效特征 维持其较高的口服生物利用度和药代动力学(PK)。 从这些研究中开发出一种新的先导化合物C203；这种化合物 其功效似乎是CPI-1189的两倍。在目前的第二阶段 建议开展更多的药效和机理研究 C203的美国IND中包含的药理包。同样计划的还有 批量药物生产，以及试点安全性和PK研究，以支持28天的GLP C203对大鼠和狗的毒性研究。这些活动都将 支持IND备案。本提案是对以前一份提案的修订 申请第二期拨款。 建议的商业应用：不可用

DESCRIPTION (Adapted from the application): The treatment and prevention of the debilitating symptoms of inflammatory bowel disease (IBD) represents a major unmet medical need. This proposal is for support of Phase II studies to further develop Centaur's lead IBD candidate. During the period of the Phase I grant the chemical structure of the lead candidate, CPI-1189 was optimized in order to improve its efficacy characteristics in an in vivo rat model of IBD while maintaining its high oral bioavailability and pharmacokinetic (PK) profile. From these studies a new lead compound, C203, was developed; this compound appears to have twice the efficacy of CPI-1189. In the present Phase II application, additional efficacy and mechanism studies are proposed to develop a pharmacology package for inclusion in a US IND for C203. Also planned are bulk drug production, and pilot safety and PK studies to support 28-day GLP toxicity studies with C203 in the rat and dog. These activities will all support an IND filing. The present proposal is a revision of a previous application for Phase II funding. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE