マブチ　ミユキ   馬渕　美雪    所属   兵庫医科大学  薬学部 医療薬学科    職種   助教
言語種別	英語
発行・発表の年月	2020/01
形態種別	学術雑誌
査読	査読あり
標題	Identification of HUHS190, a human naftopidil metabolite, as a novel anti-bladder cancer drug.
執筆形態	共著
掲載誌名	Bioorganic & medicinal chemistry letters
掲載区分	国外
巻・号・頁	30(1),pp.126744
著者・共著者	Shimizu Tadashi, Yamaguchi Keiko, Yamamoto Momoka, Kurioka Rina, Kino Yukari, Matsunaga Wataru, Nakao Syuhei, Fukuhara Hiroshi, Tanaka Akito, Gotoh Akinobu, Mabuchi Miyuki
概要	We carried out structure-activity relationship study on anti-cancer effects of naftopidil (1) and its metabolites, resulted in identification of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190), a major human metabolite of 1. 2 was more hydrophilic compared to 1, was enough to be prepared in high concentration solution of more than 100 μM in saline for an intravesical instillation drug. In this study, we estimated anticancer effects of 2 in a bladder cancer model after intravesical administration similar to clinical cases. A single intravesical administration of 2 exhibited the most potent inhibitory activities among the clinical drugs for bladder cancers, BCG and Pirarubicin, without obvious side effects and toxicity. Thus, HUHS190 can be effective for patients after post-TURBT therapy of bladder cancer without side effects, unlike the currently available clinical drugs.
DOI	10.1016/j.bmcl.2019.126744
ISSN	1464-3405
PMID	31759851