Single chain peptide agonists of relaxin receptors

Praveen, Praveen; Kočan, Martina; Valkovic, Adam L.; Bathgate, Ross A. D.; Hossain, Mohammed Akhter

doi:10.1016/j.mce.2019.01.008

Cited by 13 publications

(13 citation statements)

References 57 publications

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“…By contrast, however, B7-33 is a single-chain analog of the H2-relaxin B-chain, which retains binding to RXFP1. 35,55 B7-33 has lower binding affinity than H2-relaxin at RXFP1 but has similar potency to H2-relaxin in the activation of the phosphorylated extracellular signal-regulated kinase pathway in RXFP1expressing human embryonic kidney cells and rodent myofibroblasts. 35 Functionally, the small B7-33 peptide agonist efficiently prevented or reversed organ fibrosis and dysfunction in rodent models of heart or lung disease.…”

Section: Discussionmentioning

confidence: 98%

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Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice: behavioral and neurochemical data

Abboud

Brochoire

Drouet

et al. 2021

PR9

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Section: Discussionmentioning

confidence: 98%

“… 69 However, such biased signaling has not been observed for B7-33, which is a more selective RXFP1 agonist. 5 , 55 …”

Section: Discussionmentioning

confidence: 99%

Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice: behavioral and neurochemical data

Abboud

Brochoire

Drouet

et al. 2021

PR9

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“…Nucleus incertus relaxin‐3 neurones are responsive to peripheral and sensory and stress‐related inputs, 45 and project widely to RXFP3‐rich areas throughout the brain, where they influence arousal, 46 hypothalamic, limbic and sensory activity, 47,48 as well as spatial memory and navigation via interactions with the septohippocampal system 42,49,50 . The pharmacology of RXFP3 51 has developed progressively over the last decade, driven by the production of RXFP3‐selective chimeric, truncated, stapled and single‐chain peptides, 52,53 as well as the recent report of a potent, small organic molecule agonist 54 . These important tools, which include a viral‐based RXFP3 agonist delivery system, 55 along with a range of appropriate transgenic mouse lines, 56,57 will continue to assist proof‐of‐concept studies aiming to evaluate the involvement of RXFP3 signalling in various aspects of physiology and behaviour, and in clinical CNS disorders 58 .…”

Section: Relaxin: a Prototype ‘Brain Stem Ascending’ Regulatory Peptidementioning

confidence: 99%

Regulatory peptides and systems biology: A new era of translational and reverse‐translational neuroendocrinology

Eiden

Gundlach

Grinevich

et al. 2020

J Neuroendocrinology

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Recently, there has been a resurgence in regulatory peptide science as a result of three converging trends. The first is the increasing population of the drug pipeline with peptide-based therapeutics, mainly in, but not restricted to, incretin-like molecules for treatment of metabolic disorders such as diabetes. The second is the development of genetic and optogenetic tools enabling new insights into how peptides actually function within brain and peripheral circuits to accomplish homeostatic and allostatic regulation. The third is the explosion in defined structures of the G-protein coupled receptors to which most regulatory peptides bind and exert their actions.These trends have closely wedded basic systems biology to drug discovery and development, creating a "two-way street" on which translational advances travel from basic research to the clinic, and, equally importantly, "reverse-translational" information is gathered, about the molecular, cellular and circuit-level mechanisms of action of regulatory peptides, comprising information required for the fine-tuning of drug development through testing in animal models. This review focuses on a small group of 'influential' peptides, including oxytocin, vasopressin, pituitary adenylate cyclase-activating polypeptide, ghrelin, relaxin-3 and glucagon-like peptide-1, and how basic discoveries and their application to therapeutics have intertwined over the past decade. K E Y W O R D S neuroendocrinology, regulatory peptide, therapeutics, translation How to cite this article: Eiden LE, Gundlach AL, Grinevich V, et al. Regulatory peptides and systems biology: A new era of translational and reverse-translational neuroendocrinology.

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“…B7-33 was shown to bind to RXFP1 and preferentially activate the extracellular signal-regulated kinase (ERK) pathway over cAMP in cells that endogenously expressed RXFP1 (figure 1) [92]. In mouse models with ovalbumin-induced chronic allergic airways disease, B7-33 significantly diminished airway epithelial thickening, amount of total lung collagen (a benchmark of fibrosis), and airway hyperresponsiveness (a benchmark of lung dysfunction) to a similar magnitude to native relaxin-2 [93]. An alternative approach is to target RXFP1 using small molecules that act as either agonists or alternatively augment the agonist activity of relaxin-2 as positive allosteric modulators [86].…”

Section: Agonists Of the Relaxin Receptormentioning

confidence: 99%

The future of bronchodilation: looking for new classes of bronchodilators

2019

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@ERSpublicationsThere is a real interest among researchers and the pharmaceutical industry in developing novel bronchodilators. There are several new opportunities; however, they are mostly in a preclinical phase. They could better optimise bronchodilation. http://bit.ly/2lW1q39Cite this article as: Cazzola M, Rogliani P, Matera MG. The future of bronchodilation: looking for new classes of bronchodilators.ABSTRACT Available bronchodilators can satisfy many of the needs of patients suffering from airway disorders, but they often do not relieve symptoms and their long-term use raises safety concerns. Therefore, there is interest in developing new classes that could help to overcome the limits that characterise the existing classes. At least nine potential new classes of bronchodilators have been identified: 1) selective phosphodiesterase inhibitors; 2) bitter-taste receptor agonists; 3) E-prostanoid receptor 4 agonists; 4) Rho kinase inhibitors; 5) calcilytics; 6) agonists of peroxisome proliferator-activated receptor-γ; 7) agonists of relaxin receptor 1; 8) soluble guanylyl cyclase activators; and 9) pepducins. They are under consideration, but they are mostly in a preclinical phase and, consequently, we still do not know which classes will actually be developed for clinical use and whether it will be proven that a possible clinical benefit outweighs the impact of any adverse effect.It is likely that if developed, these new classes may be a useful addition to, rather than a substitution of, the bronchodilator therapy currently used, in order to achieve further optimisation of bronchodilation.

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Single chain peptide agonists of relaxin receptors

Cited by 13 publications

References 57 publications

Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice: behavioral and neurochemical data

Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice: behavioral and neurochemical data

Regulatory peptides and systems biology: A new era of translational and reverse‐translational neuroendocrinology

The future of bronchodilation: looking for new classes of bronchodilators

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