Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice

European Journal of Pharmacology
Makoto YoshimuraTakao Tanaka

Abstract

Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC50) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenu...Continue Reading

Citations

Jul 19, 2018·Minerva gastroenterologica e dietologica·Roberto de SireFranco Scaldaferri
Sep 3, 2019·Biological & Pharmaceutical Bulletin·Hiroshi WatanabeToru Maruyama
Nov 5, 2019·Frontiers in Oncology·Saeed Soleyman-JahiKazem Zendehdel
Feb 20, 2020·International Journal of Molecular Sciences·Elena ConteAntonella Liantonio
Nov 15, 2019·Journal of Applied Physiology·Megan E Rosa-CaldwellNicholas P Greene

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