Delving into the Latest Updates on YIL-781 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

GHSR

Mechanism

GHSR antagonists(Ghrelin/growth hormone secretagogue receptor antagonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus

Inactive Indication-

Originator Organization

Bayer Healthcare Co., Ltd.

Active Organization

Bayer Healthcare Co., Ltd.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC24H28FN3O2

InChIKeyFRKXOBMDEXCHHD-SFHVURJKSA-N

CAS Registry875258-85-8

Background and PurposeSome agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and the pharmacology of the receptors are unknown.Experimental ApproachThe effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfected with the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a).Key ResultsThree agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in the anaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity. Early hypotension was not reduced by hexamethonium or by baroreceptor (sino‐aortic) denervation. Ulimorelin also relaxed isolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55 and 7.84.Conclusions and ImplicationsOur results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709 lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin.

100 Deals associated with YIL-781

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