The role of selective brain penetrating GRPR antagonists in pruritis.

描述（由申请人提供）：目的是发现新型选择性GRP受体（GRPR）CNS渗透拮抗剂作为探针，以验证与炎症反应有关的新靶点。在这项工作中，将确定新的化合物，利用我们的试验级联结合体外受体药理学和新的体内筛选工具，以评估药理学行为。候选配体将使用药物化学中一系列公认的方法设计和合成，以具有较高的CNS渗透可能性。将在一系列临床前尿道炎模型中评估符合我们的体外标准的化合物，以评价该受体在尿道炎中的作用。这项工作将确定GRPR参与炎症反应，并确定其作为潜在药物靶点的效用。 公共卫生相关性：目的是发现和开发新的探针，用于验证肠炎的新机制，这是不适的主要原因。

DESCRIPTION (provided by applicant): The goal is to discover novel selective CNS penetrant antagonists of the GRP receptor (GRPR) as probes to validate a new target implicated in pruritic responses. In this work, new compounds will be identified utilizing our assay cascade incorporating in vitro receptor pharmacology and novel in vivo screening tools for evaluating pruritic behavior. Candidate ligands will be designed and synthesized using a series of recognized approaches in medicinal chemistry to have a high likelihood of CNS penetration. Compounds that meet our in vitro criteria will be assessed in a series of pre-clinical pruritis models to evaluate the role of this receptor in pruritis. This work will determine the involvement of GRPR in the pruritic response and determine its utility as a potential drug target. PUBLIC HEALTH RELEVANCE: The objective is to discover and develop new probes for the validation of a new mechanism in pruritis, a leading cause of discomfort.