UFP-101, a Peptide Antagonist Selective for the Nociceptin/Orphanin FQ Receptor

Girolamo Calo, Remo Guerrini, Anna Rizzi, Severo Salvadori, Melissa Burmeister, Daniel R. Kapusta, David G. Lambert, Domenico Regoli
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引用次数: 99

Abstract

Nociceptin/orphanin FQ modulates various biological functions at central and peripheral levels by selectively activating a G-protein coupled receptor named N/OFQ peptide (NOP) receptor. For extending our knowledge on the biological roles of the N/OFQ - NOP receptor system the identification of selective NOP ligands, especially antagonists, is mandatory. [Nphe1, Arg14, Lys15] N/OFQ-NH2 (UFP-101) is a novel NOP ligand that was designed by combining, in the same molecule, the [Nphe1] chemical modification which eliminates efficacy and the [Arg14, Lys15] substitution which increases ligand potency and duration of action in vivo. In the present article, we summarize the pharmacological features of UFP-101 as determined in a series of in vitro and in vivo assays. Moreover, some biological actions and possible therapeutic indications of NOP ligands are discussed on the basis of results obtained with UFP-101. Data obtained with this compound were compared with those generated using other NOP antagonists, especially J-113397 and [Nphe1]N/OFQ(1-13)-NH2, receptor or peptide knockout mice and other pharmacological tools useful for blocking N/OFQ – NOP receptor signaling.

The analysis of the available data demonstrates that UFP-101 is a useful pharmacological tool for the investigation of the central and peripheral biological functions regulated by the N/OFQ – NOP receptor system and for defining the therapeutic potential of NOP receptor ligands

UFP-101,一种选择性的肽拮抗剂Nociceptin/Orphanin FQ受体
Nociceptin/orphanin FQ通过选择性激活一种名为N/OFQ肽(NOP)受体的g蛋白偶联受体,在中枢和外周水平调节多种生物功能。为了扩大我们对N/OFQ - NOP受体系统生物学作用的认识,鉴定选择性NOP配体,特别是拮抗剂是必要的。[Nphe1, Arg14, Lys15] N/OFQ-NH2 (UFP-101)是一种新型的NOP配体,它是通过在同一分子中结合[Nphe1]化学修饰(消除药效)和[Arg14, Lys15]取代(增加配体在体内的效力和作用时间)而设计的。在这篇文章中,我们总结了UFP-101的药理学特征,通过一系列体外和体内试验确定。此外,根据UFP-101的研究结果,讨论了NOP配体的一些生物学作用和可能的治疗适应症。将该化合物获得的数据与其他NOP拮抗剂(特别是J-113397和[Nphe1]N/OFQ(1-13)- nh2)、受体或肽敲除小鼠以及其他可阻断N/OFQ - NOP受体信号传导的药理学工具产生的数据进行比较。对现有数据的分析表明,UFP-101是研究N/OFQ - NOP受体系统调节的中枢和外周生物学功能以及确定NOP受体配体治疗潜力的有用药理学工具
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