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Can I read Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer on EtoBox?
Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer by Satoshi Endo; Hiroaki Oguri; Jin Segawa; Mina Kawai; Dawei Hu; Shuang Xia; Takuya Okada; Katsumasa Irie; Shinya Fujii; Hiroaki Gouda; Kazuhiro Iguchi; Takuo Matsukawa; Naohiro Fujimoto; Toshiyuki Nakayama; Naoki Toyooka; Toshiyuki Matsunaga; Akira Ikari is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer about?
Aldo-keto reductase (AKR) 1C3 catalyzes the synthesis of active androgens that promote the progression of prostate cancer. AKR1C3 also contributes to androgen-independent cell proliferation and survival through the metabolism of prostaglandins and reactive aldehydes. Because of its elevation in castration-resistant prostate cancer (CRPC) tissues, AKR1C3 is a promising therapeutic target for CRPC. In this study, we found a novel potent AKR1C3 inhibitor, -(4-fluorophenyl)-8-hydroxy-2-imino-2-chromene-3-carboxamide (), and synthesized its derivatives with IC values of 25-56 nM and >220-fold selectivity over other AKRs (1C1, 1C2, and 1C4). The structural factors for the inhibitory potency were elucidated by crystallographic study of AKR1C3 complexes with and . The inhibitors suppressed proliferation of prostate cancer 22Rv1 and PC3 cells through both androgen-dependent and androgen-independent mechanisms. Additionally, and prevented prostate tumor growth in a xenograft mouse model. Furthermore, the inhibitors significantly augmented apoptotic cell death induced by anti-CRPC drugs (abiraterone or enzalutamide).
Who reads Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Satoshi Endo; Hiroaki Oguri; Jin Segawa; Mina Kawai; Dawei Hu; Shuang Xia; Takuya Okada; Katsumasa Irie; Shinya Fujii; Hiroaki Gouda; Kazuhiro Iguchi; Takuo Matsukawa; Naohiro Fujimoto; Toshiyuki Nakayama; Naoki Toyooka; Toshiyuki Matsunaga; Akira Ikari
- Publisher
- American Chemical Society (ACS)
- Published
- 2020
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)