Design and synthesis of novel selective estrogen receptor degradation inducers based on the diphenylheptane skeleton.

Autor: Misawa T; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Fujisato T; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Kanda Y; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Ohoka N; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Shoda T; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Yorioka M; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Makishima M; Nihon University Itabashi , Tokyo , 173-8610 , Japan., Sekino Y; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Naito M; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Demizu Y; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp., Kurihara M; National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email: misawa@nihs.go.jp ; Email: masaaki@nihs.go.jp.
Jazyk: angličtina
Zdroj: MedChemComm [Medchemcomm] 2016 Dec 08; Vol. 8 (1), pp. 239-246. Date of Electronic Publication: 2016 Dec 08 (Print Publication: 2017).
DOI: 10.1039/c6md00553e
Abstrakt: Estrogen receptors (ERs) are a family of nuclear receptors (NRs) that regulate physiological effects such as reproduction and bone homeostasis. It has been reported that approximately 70% of human breast cancers are hormone-dependent and ERα-positive. Recently, novel anti-breast cancer drugs based on different mechanisms of action have received significant attention. In this article, we have designed and synthesized a selective ER degradation inducer based on the diphenylheptane skeleton. Western blotting analysis revealed that PBP-NC10 degraded ERα through the ubiquitin-proteasome system. We also performed computational docking analysis to predict the binding mode of PBP-NC10 to ERα.
Databáze: MEDLINE
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