Illuminating Orphan GPCRs in Lymphatics

摘要 由于超过40%的临床可用药物靶向G蛋白偶联受体（GPCR）， 人们对了解更多关于这个蛋白质家族的信息非常感兴趣， 治疗目标当考虑到人类基因编码的不同种类的蛋白质时， 基因组被预测是药理学上易处理的，一个显着的四分之一代表 GPCR。然而，在约345种无气味的GPCR中，很大一部分仍然是无气味的， 已知配体-或具有未表征的生理功能。因为我们缺乏 淋巴管的药理学靶点，有理由集中精力探索 并描述淋巴“GPCRome”是一个值得的奋进。我们已经确定了3个 作为可药用基因组中IDG合格靶蛋白的孤儿GPCR (IDG)项目我们建议开发和使用体外和基于动物的系统， 表征这些GPCR在淋巴管系统中的表达和活化。我们 结果将进一步推动IDG联盟的总体目标，并揭示新的生理 的调节途径和潜在的治疗靶点，这仍然是一个 研究不足，临床需求未得到满足。

ABSTRACT Since more than 40% of all clinically-available drugs target G-protein coupled receptors (GPCRs), there is great interest in learning more about this family of proteins in order to discover new therapeutic targets. When considering the different classes of proteins encoded by the human genome that are predicted to be pharmacologically-tractable, a remarkable one quarter represent GPCRs. And yet, of the ~345 non-odorant GPCRs a large proportion remain orphan—with no known ligand—or have uncharacterized physiological functions. Since we have a dearth of pharmacological targets for lymphatic vessels, it stands to reason that focused efforts to explore and characterize the lymphatic “GPCRome” is a worthwhile endeavor. We have identified 3 orphan GPCRs that are IDG-eligible target proteins in the Illuminating the Druggable Genome (IDG) Project. We propose to develop and use in vitro and animal-based systems to further characterize the expression and activation of these GPCRs in the lymphatic vasculature. Our results will further the overall goals of the IDG Consortium and reveal novel physiological pathways and potential therapeutic targets for the modulation of lymphatics, which remains an understudied research area with unmet clinical needs.