マブチ　ミユキ   MIYUKI MABUCHI   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	2014/02
形態種別	学術雑誌
標題	Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs.
執筆形態	共著
掲載誌名	Bioorganic & medicinal chemistry letters
掲載区分	国外
巻・号・頁	24(4),pp.1071-4
著者・共著者	Nakao Syuhei, Mabuchi Miyuki, Shimizu Tadashi, Itoh Yoshihiro, Takeuchi Yuko, Ueda Masahiro, Mizuno Hiroaki, Shigi Naoko, Ohshio Ikumi, Jinguji Kentaro, Ueda Yuko, Yamamoto Masatatsu, Furukawa Tatsuhiko, Aoki Shunji, Tsujikawa Kazutake, Tanaka Akito
概要	A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4-dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using a recombinant PCA-1/ALKBH3, 1-(1H-5-methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H-pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral administration. As expected, continuously administering 35 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.
DOI	10.1016/j.bmcl.2014.01.008
ISSN	1464-3405
PMID	24461353