Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10587080 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
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.
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Syuhei Nakao, Miyuki Mabuchi, Tadashi Shimizu, Yoshihiro Itoh, Yuko Takeuchi, Masahiro Ueda, Hiroaki Mizuno, Naoko Shigi, Ikumi Ohshio, Kentaro Jinguji, Yuko Ueda, Masatatsu Yamamoto, Tatsuhiko Furukawa, Shunji Aoki, Kazutake Tsujikawa, Akito Tanaka,