The role of selective brain penetrating GRPR antagonists in pruritis.

描述（由申请人提供）：目标是发现GRP受体（GRPR）的新型选择性CNS渗透拮抗剂作为探针，以验证与瘙痒反应有关的新靶点。在这项工作中，新的化合物将利用我们的实验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。候选配体将使用一系列药物化学中公认的方法来设计和合成具有高可能性穿透中枢神经系统的配体。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在瘙痒反应中的作用，并确定其作为潜在药物靶点的效用。

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.