EP1572: A novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man

Broglio, Fabio; Boutignon, F.; Benso, Andrea; Gottero, Cristina; Prodam, Flavia; Arvat, Emanuela; Ghè, Corrado; Catapano, Filomena; Torsello, Antonio; Locatelli, Vittorio; Muccioli, Giampiero; Boeglin, Damien; Guerlavais, Vincent; Fehrentz, Jean Alaín; Martinez, Jean; Ghigo, Ezio; Deghenghi, Romano

doi:10.1007/bf03345096

Cited by 45 publications

(48 citation statements)

References 8 publications

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“…[8][9][10] All attempts to replace the Aib residue resulted in less potent compounds, indicating the significance of this residue for the stimulation of GH secretion. Recently, we reported that 1,2,4-triazole was a good scaffold to obtain potent GHS-R1a ligands of the ghrelin receptor, leading to agonists, partial agonists, or antagonists.…”

Section: Chemistrymentioning

confidence: 99%

Toward Potent Ghrelin Receptor Ligands Based on Trisubstituted 1,2,4-Triazole Structure. 2. Synthesis and Pharmacological in Vitro and in Vivo Evaluations

et al. 2007

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A series of ghrelin receptor ligands based on the trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the significance of the aminoisobutyryl (Aib) moiety, a common feature in numerous growth hormone secretagogues described in the literature. Potent agonist and antagonist ligands of the growth hormone secretagogue receptor type 1a (GHS-R1a) were obtained, i.e., compounds 41 (JMV2894) and 17 (JMV3031). The best compounds were evaluated for their in vivo activity on food intake, after sc injection in rodents. Among the tested compounds, few of them were able to stimulate food intake and some others, i.e., compounds 4 (JMV2959), 17, and 52 (JMV3021), acted as potent in vivo antagonist of hexarelin-stimulated food intake. These compounds did not stimulate growth hormone secretion in rats and furthermore did not antagonize growth hormone secretion induced by hexarelin, revealing that it is possible to modulate food intake without altering growth hormone secretion.

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Section: Chemistrymentioning

confidence: 99%

Toward Potent Ghrelin Receptor Ligands Based on Trisubstituted 1,2,4-Triazole Structure. 2. Synthesis and Pharmacological in Vitro and in Vivo Evaluations

et al. 2007

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“…BIM-28131, a small peptide ghrelin agonist, and BIM-28163, a full-length ghrelin analog antagonist were used in some studies on hypothalamic actions of ghrelin [228]. Also, some peptidomimetics have been produced including the pseudotripeptide EP01572 (H-Aib-(D)-Trp-(D)-gTrp-formyl) with increased stability and oral bioavailability [229] even in human [230], and JMV 1843 [231] shown in (Fig. 5A).…”

Section: Ghrelinmentioning

confidence: 99%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre-and postsynaptically. Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed, a number of neuropeptides have been implicated in epilepsy and many of them are considered to have endogenous neuroprotective actions. Neuropeptides, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic substances. Hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy are discussed in the review article. Oral application of neuropeptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration through the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors as well as gene therapeutic approaches leading to the local production of neuropeptides within the central nervous system will also be discussed.

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“…By counting neurons, we found a better preservation of cellularity in regions in which damage was more pronounced, such as the hilus of dentate gyrus and the layer III of medial entorhinal cortex, only in rats treated with JMV-1843. The beneficial findings observed with JMV-1843 administration were probably related to the advantageous pharmacokinetics of this drug when compared to ghrelin [79,80].…”

Section: Is Vascular Protection An Affordable Goal For Treatment Of Smentioning

confidence: 90%

Ischemic–hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus

Lucchi

Vinet

Meletti

et al. 2015

Epilepsy & Behavior

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EP1572: A novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man

Cited by 45 publications

References 8 publications

Toward Potent Ghrelin Receptor Ligands Based on Trisubstituted 1,2,4-Triazole Structure. 2. Synthesis and Pharmacological in Vitro and in Vivo Evaluations

Toward Potent Ghrelin Receptor Ligands Based on Trisubstituted 1,2,4-Triazole Structure. 2. Synthesis and Pharmacological in Vitro and in Vivo Evaluations

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Ischemic–hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus

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