RATIONAL DESIGN OF ADHESION BLOCKING ANTI-INFLAMMATORIES

描述：(改编自《调查者摘要》) 人类的许多慢性和急性疾病已被证明具有 被称为选择素的细胞黏附分子的实质性参与。这个 选择素介导白细胞募集到组织部位以促进 感染性休克的炎性损伤，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 哮喘和牛皮癣等疾病。这个项目的目标是 建立有效的选择素抑制剂的有效性和安全性数据以吸引 风险投资和/或制药合作伙伴推动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，一组定义的多聚体选择素 配体类似物在紫外光稳定的脂质体上的表达称为PLN 在人类细胞剪切分析系统中作为选择素抑制剂有效，并在 老鼠。在这个第二阶段的提案中，调查人员试图优化 用于综合研究的PLN类药物的配方和合成 人类哮喘和牛皮癣动物模型的研究 密歇根大学。这些研究将作为 毒理学和药代动力学研究将有助于制备PLN 治疗公司申请IND/CTX。 建议的商业应用：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