Novel Class Therapy for IPF

摘要特发性肺纤维化(Ipf)是最致命的肺部疾病之一，死亡率高，病死率极低。 治疗方案。在IPF患者的肺中发现胶原蛋白的产生增加。不幸的是，目前的FDA- 批准的治疗方法不能阻止疾病的发展。体外和体内的概念验证研究已经被 由我公司完成，证明了抑制肽基-Pro-异构酶可以有效地 减少胶原生成和最终纤维化肺重塑的策略。因此，我们设计了一种 基于4-氨基酸骨架的新化合物的探索性文库以开发这一治疗策略。输出 在24个新化合物中的前8个化合物中，有一个已经显示出高度有效的抑制胶原生成的作用。 通过人类成纤维细胞。此第一阶段SBIR提案将通过确定最佳 化合物及其在体外和体内模型中的治疗概念验证(目标1)和通过 鉴定和提纯从目标1预先存在的库中鉴定出的最佳化合物，以获得最佳PK图谱 (AIM2)。当这些里程碑完成时，这些新化合物预计将准备好 进入治疗开发的前IND阶段。

Idiopathic pulmonary fibrosis (IPF) is one of the most fatal lung diseases with high mortality and very limited treatment options. Increased production of collagen is found in IPF patients’ lung. Unfortunately current FDA- approved treatments do not stop disease progression. In vitro and in vivo proof-of-concept studies have been completed by our company and demonstrated that inhibiting peptidyl-prolyl-isomerase can be an effective strategy to reduce collagen production and eventual fibrotic lung remodeling. Therefore, we have designed an exploratory library of novel compounds based on 4-amino acid backbone to exploit this therapeutic strategy. Out of the first eight of the 24 novel compounds, one has already shown highly active inhibition of collagen production by human fibroblasts. This Phase 1 SBIR proposal will further develop this technology by identifying the best compound and establishing its therapeutic proof-of-concept in in vitro and in vivo modeling (Aim 1) and by identifying and refining the best compound identified from the Aim 1 pre-existing library for the optimal PK profile (Aim2). When these milestones are accomplished, these new compounds are anticipated to become ready for entering the pre-IND phase of therapeutic development.