Selection of a lead candidate for the development of a novel anti-inflammatory therapeutic

项目摘要/摘要 皮尔治疗公司(PEEL)正在开创一种预防发病率和死亡率的新方法 通过抑制中性粒细胞胞外陷阱与炎症性疾病相关 (篮网)。Net是用组蛋白和抗菌剂装饰的去浓缩染色质的晶格 由多形核白细胞(PMN)挤出的蛋白质，以捕获和杀死微生物。而当 调节的网络形成包含感染，调节的网络形成导致炎症 组织损伤和血管损伤。Net与人类疾病有牵连， 由炎症引起，包括败血症、中风、糖尿病和心脏病。网络的能力-- 阻止PMN依赖的网络形成的抑制因子(NIF)使这一新的描述 一类内源性多肽--治疗因病和/或疾病的良好药物 网络依赖的炎症事件加剧了这种情况。在第一阶段SBIR中，PEELL将量化 并比较两种NIF的体内外生物活性和药代动力学。这个 先导NIF多肽将在抗网络治疗方面取得新的进展。之后 完成这些SBIR第一阶段任务后，Peel Treateutics将处于极好的地位 将其基于NIF的新专利疗法推进到进一步的临床前研究。这些努力 By Peel Treateutics有可能破坏和改进这两种疾病的治疗方法 急慢性炎症性疾病。

PROJECT SUMMARY/ABSTRACT PEEL Therapeutics, Inc. (PEEL) is pioneering a novel approach to prevent morbidity and mortality associated with inflammatory disease through the inhibition of neutrophil extracellular traps (NETs). NETs are lattices of decondensed chromatin decorated with histones and antimicrobial proteins extruded by polymorphonuclear leukocytes (PMNs) to trap and kill microbes. While regulated NET formation contains infection, dysregulated NET formation leads to inflammatory tissue damage and vascular injury. NETs have been implicated in human diseases characterized by inflammation, including sepsis, stroke, diabetes, and heart disease. The ability of NET- inhibitory factors (NIFs) to block PMN-dependent NET formation makes this newly described class of endogenous peptides a promising therapeutic modality for diseases caused and/or exacerbated by NET-dependent inflammatory events. In this Phase I SBIR, PEEL will quantify and compare the biological activity and pharmacokinetics of two NIFs in vitro and in vivo. The lead NIF peptide will move forward in the development of a novel anti-NET therapeutic. After completing these SBIR Phase I tasks, PEEL Therapeutics will be in an excellent position to advance its new and patented NIF-based therapeutic to further preclinical studies. These efforts by PEEL Therapeutics hold the potential to disrupt and improve the treatment approach to both acute and chronic inflammatory diseases.