RATIONAL DESIGN OF ADHESION BLOCKING ANTI-INFLAMMATORIES

描述：（改编自研究者摘要） 许多慢性和急性疾病的人已被证明有 细胞粘附分子，即选择素的大量参与。的 选择素介导白细胞募集到组织部位， 感染性休克，缺血-再灌注损伤， 急性呼吸窘迫综合征和各种慢性免疫过敏性 哮喘和牛皮癣等疾病。该项目的目标是 建立有效选择素抑制剂的有效性和安全性数据， 风险投资和/或制药合作伙伴，以推进PLN疗法 通过I期和II期临床试验。通过初步的第一阶段研究， 研究人员已经证明，一组确定的多聚化选择素 在称为PLN的UV稳定脂质体上表达的配体类似物非常 在人细胞剪切测定系统中和在 小鼠在第二阶段的提案中，研究人员寻求优化 用于综合研究的基于PLN的治疗剂的配制和合成 人类哮喘和银屑病的动物模型， 密歇根大学。这些研究将作为 用于制备PLN的毒理学和药代动力学研究 用于提交IND/CTX的治疗剂。 拟议商业应用：不可用

DESCRIPTION: (Adapted from the Investigator's Abstract) The pathogenesis of many chronic and acute diseases of man has been demonstrated to have substantial involvement of cellular adhesion molecules known as selectins. The selectins mediate leukocyte recruitment into tissue sites to promote inflammatory injuries that underlies septic shock, ischemia-reperfusion injury, acute respiratory distress syndrome, and various chronic immune allergic disorders such as asthma and psoriasis. The goal of this project is to establish efficacy and safety data for potent selectin inhibitors to attract venture capital and/or a pharmaceutical partner to advance the PLN therapeutics through Phase I and II clinical trials. Through preliminary Phase I study the investigators have demonstrated that a defined group of multimerized selectin ligand analog expresses on UV-stabilized lyposomes termed PLN are very effective as selectin inhibitors in human cell shear assays systems and in mice. In this Phase II proposal the investigators seek to optimize the formulation and synthesis of PLN based therapeutics for comprehensive studies of animal models of human asthma and psoriasis in collaboration with the University of Michigan. These studies will serve as the basis for the toxicological and phramacokinetic studies that will serve to prepare PLN therapeutics for filing an IND/CTX. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE