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New directions for urotensin II receptor ligands

Abstract : The urotensinergic system, formed by a G protein‐coupled receptor (GPCR) termed UT and two endogenous peptide ligands Urotensin II (UII, H‐Glu‐Thr‐Pro‐Asp‐[Cys‐Phe‐Trp‐Lys‐Tyr‐Cys]‐Val‐OH) and Urotensin II‐related peptide (URP, H‐Ala‐[Cys‐Phe‐Trp‐Lys‐Tyr‐Cys]‐Val‐OH), is currently regarded as a potential key contributor to cardiovascular functions. While multiple animal studies have shown the therapeutic potential of UT ligands for the treatment of heart failure and atherosclerosis, their lack of efficacy in clinical studies points toward a greater understanding of UT pharmacology at both the molecular and cellular levels. UII and URP are cyclic peptides that share a common and strictly conserved bioactive cyclic core (‐Cys‐Phe‐Trp‐Lys‐Tyr‐Cys‐) but differ by their extracyclic N‐terminal residues. While sharing common biological activity, these two endogenous ligands appear to be functionally selective, displaying different specific effects through the selection/stabilization of particular UT active conformations. Thus, UII and URP should be regarded as two distinct actors in the control of cardiovascular functions. In this regard, more focus on URP biological effects had to be paid, while systematic evaluation of new antagonists against both endogenous ligands appears mandatory. Overall, this review offers an overview of the actual horizon of UT pharmacology, notably concerning the development of biased ligands and allosteric modulators.
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https://hal-riip.archives-ouvertes.fr/pasteur-02133250
Contributor : Michel Courcelles <>
Submitted on : Friday, May 17, 2019 - 9:10:31 PM
Last modification on : Wednesday, August 14, 2019 - 3:24:01 PM

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Etienne Billard, Étienne Billard, Mustapha Iddir, Hassan Nassour, Laura Lee-Gosselin, et al.. New directions for urotensin II receptor ligands. Peptide Science, John Wiley & Sons, Ltd, 2018, 111 (1), pp.e24056. ⟨10.1002/pep2.24056⟩. ⟨pasteur-02133250⟩

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