The role of selective brain penetrating GRPR antagonists in pruritis.

描述(由申请人提供)：目标是发现新的选择性中枢神经系统GRP受体穿透性拮抗剂(GRPR)作为探针，以验证与瘙痒反应有关的新靶点。在这项工作中，将利用我们的试剂级联结合体外受体药理学和新的体内筛选工具来评估瘙痒行为，从而识别新的化合物。候选配体将使用药物化学中公认的一系列方法来设计和合成，以具有很高的中枢神经系统渗透的可能性。符合我们体外标准的化合物将在一系列临床前瘙痒模型中进行评估，以评估该受体在瘙痒中的作用。这项工作将确定GRPR在瘙痒反应中的参与，并确定其作为潜在药物靶点的效用。 公共卫生相关性：目标是发现和开发新的探索，以验证瘙痒炎的新机制，瘙痒炎是导致不适的主要原因。

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.