Safety evaluation of FM101, an A3 adenosine receptor modulator, in rat, for developing as therapeutics of glaucoma and hepatitis

Park, Chong-Woo; Han, Chung-Tack; Sakaguchi, Yasue; Lee, Jiyoun; Youn, Hwa-Young

Safety evaluation of FM101, an A3 adenosine receptor modulator, in rat, for developing as therapeutics of glaucoma and hepatitis

dc.contributor.author	Park, Chong-Woo
dc.contributor.author	Han, Chung-Tack
dc.contributor.author	Sakaguchi, Yasue
dc.contributor.author	Lee, Jiyoun
dc.contributor.author	Youn, Hwa-Young
dc.date.accessioned	2020-05-26T14:02:39Z
dc.date.available	2020-05-26T14:02:39Z
dc.date.issued	2020-02-12
dc.description.abstract	Adenosine is a critical regulator of inflammation and fibrosis, it affects endogenous cell signaling via binding to the A3 adenosine receptor. FM101 is a potent, highly selective A3 adenosine receptor modulator that has been developed as a treatment for glaucoma and hepatitis. We determined that FM101 is a biased ligand with functional activities both as a G protein agonist and a β-arrestin antagonist. The safety of FM101 was evaluated by administering an acute dose in rats, the results indicated that the approximate lethal dose was greater than 2000 mg/kg. In a subchronic toxicity study, FM101 was administered orally once per day to rats at doses of 250, 500, and 1000 mg/kg/day over a period of 28 days. Abnormal posture, irregular respiration, decreased movement, and ear flushing were observed during the early phase of dosing, and loose stools were observed sporadically among the animals that received 500 and 1000 mg/kg/day. Body weight and food consumption were decreased in one male and one female rat in the 1000 mg/kg/day group during the first 2 weeks of observation. However, there were no test substance-related changes or adverse effects observed during our ophthalmological, clinical chemistry, urine, organ weight, and histopathological analysis. These findings indicate that no observed adverse effect level of FM101 was 1000 mg/kg/day in male and female rats.	en
dc.identifier.issn	1611-2156
dc.identifier.uri	http://hdl.handle.net/2003/39152
dc.identifier.uri	http://dx.doi.org/10.17877/DE290R-21070
dc.language.iso	en	de
dc.relation.ispartofseries	EXCLI Journal;Vol. 19 2020
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Adenosine	en
dc.subject	A3AR modulator	en
dc.subject	Acute oral toxicity	en
dc.subject	28-day subchronic toxicity	en
dc.subject.ddc	610
dc.title	Safety evaluation of FM101, an A3 adenosine receptor modulator, in rat, for developing as therapeutics of glaucoma and hepatitis	en
dc.type	Text	de
dc.type.publicationtype	article	de
dcterms.accessRights	open access
eldorado.dnb.zdberstkatid	2132560-1
eldorado.secondarypublication	true	de