Abstract
The nociceptin/orphanin FQ (N/OFQ)-N/OFQ peptide (NOP) receptor system is widely distributed at both the peripheral and central level where it modulates important biological functions with increasing therapeutic implications. This chapter wants to provide a comprehensive and updated overview focused on the available structure–activity relationship studies on NOP receptor peptide ligands developed through different rational approaches. Punctual modifications and cyclizations of the N/OFQ sequence have been properly combined furnishing potent NOP selective ligands with different pharmacological activities (full and partial agonists, pure antagonists) and enhanced metabolic stability in vivo. The screening of peptide libraries provided a second family of NOP ligands that have been successfully optimized. Moreover, recent findings suggest the possibility to apply different multimerization strategies for the realization of multi-target NOP/opioid receptor ligands or tetrabranched N/OFQ derivatives with extraordinarily prolonged duration of action in vivo. The diverse approaches led to the identification of important pharmacological tools along with drug candidates currently in clinical development such as Rec 0438 (aka UFP-112) for the treatment of overactive bladder and SER 100 (aka ZP120) for the clinical management of systolic hypertension.
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Author Contributions
DP, GC, and RG wrote the chapter and approved its final version.
Declaration of Interests
DP has nothing to declare. GC and RG are inventors of the patent applications WO2006/087340 and U.S. Serial No. 14/782,578 covering UFP-112 and PWT derivatives of N/OFQ, respectively, and are among the founders of the University of Ferrara spin-off company UFPeptides s.r.l., the assignee of these patents.
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Preti, D., Caló, G., Guerrini, R. (2018). NOP-Targeted Peptide Ligands. In: Ko, MC., Caló, G. (eds) The Nociceptin/Orphanin FQ Peptide Receptor. Handbook of Experimental Pharmacology, vol 254. Springer, Cham. https://doi.org/10.1007/164_2018_198
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