YIL 781 is a selective ghrelin receptor (GHSR1a) antagonist with a Ki value of 17 nM[1]. YIL 781 inhibits ghrelin-induced calcium response and improves glucose homeostasis in rats[2]. Oral administration of YIL 781 to insulin-resistant diet-induced obesity (DIO) rats reduces blood glucose fluctuations[3].
In vitro, pretreatment of GHSR1a-expressing HEK-293T cells with YIL 781 (1µM) for 10min completely reversed ghrelin-mediated forskolin-induced decrease in cAMP levels (approximately 25%)[4]. Pretreatment of primary cultures of striatal neurons with YIL 781 (2µM) antagonized the GHSR1a signaling pathway induced by auxin-releasing peptide[5].
In vivo, intraperitoneal injection of YIL 781 (5mg/kg/day) in mice for 1 week significantly inhibited prostate enlargement induced by a high-fat diet and testosterone propionate (TP)[6]. YIL 781 (3mg/kg) reversed the effect of ulimorelin on renal sympathetic nerve activity (RSNA) in rats by intravenous injection[7].
References:
[1] Esler W P, Rudolph J, Claus T H, et al. Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss[J]. Endocrinology, 2007, 148(11): 5175-5185.
[2] Perdonà E, Faggioni F, Buson A, et al. Pharmacological characterization of the ghrelin receptor antagonist, GSK1614343 in rat RC-4B/C cells natively expressing GHS type 1a receptors[J]. European journal of pharmacology, 2011, 650(1): 178-183.
[3] Sangiao-Alvarellos S, Cordido F. Effect of ghrelin on glucose‐insulin homeostasis: therapeutic implications[J]. International Journal of Peptides, 2010, 2010(1): 234709.
[4] Lillo J, Lillo A, Zafra D A, et al. Identification of the ghrelin and cannabinoid CB2 receptor heteromer functionality and marked upregulation in striatal neurons from offspring of mice under a high-fat diet[J]. International journal of molecular sciences, 2021, 22(16): 8928.
[5] Aguinaga D, Medrano M, Cordomí A, et al. Cocaine blocks effects of hunger hormone, ghrelin, via interaction with neuronal sigma-1 receptors[J]. Molecular neurobiology, 2019, 56(2): 1196-1210.
[6] Gu M, Liu C, Yang T Y, et al. High-fat diet induced gut microbiota alterations associating with Ghrelin/Jak2/Stat3 up-regulation to promote benign prostatic hyperplasia development[J]. Frontiers in cell and developmental biology, 2021, 9: 615928.
[7] Callaghan B, Kosari S, Pustovit R V, et al. Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor[J]. British Journal of Pharmacology, 2014, 171(5): 1275-1286.
















