PMID- 33415022
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210111
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 10
IP  - 12
DP  - 2020
TI  - A new compound targets the AF-1 of androgen receptor and decreases its activity 
      and protein levels in prostate cancer cells.
PG  - 4607-4623
AB  - Increased expression levels of constitutively active androgen receptor splice 
      variants (AR-Vs) cause alterations in AR signaling, resulting in drug resistance 
      and failed hormone therapy among patients with advanced prostate cancers. Several 
      available compounds targeting the androgen axis and AR signaling have not 
      demonstrated efficacy in preventing prostate cancer recurrence. Here, we 
      investigated whether a new agent, 
      6-[6-ethoxy-5-ispropoxy-3,4-dihydroisoquinolin-2[1H)-yl]-N-[6-methylpyridin-2-yl]nicotinamide 
      (EIQPN), has the potential for treating advanced prostate cancer. EIQPN 
      interacted with the AR-activation fragment-1 (AF-1) domain and blocked its 
      androgen-independent activity, robustly decreased the protein levels of AR and 
      variants in prostate cancer cells by inducing AR protein degradation, and 
      inhibited the androgen-independent proliferation of various AR-positive prostate 
      cancer cells. In xenograft mouse models, EIQPN blocked the tumor growth of 
      androgen-independent prostate cancer cells. Overall, these findings indicate that 
      EIQPN could serve as a novel therapeutic agent for advanced recurrent prostate 
      cancers.
CI  - AJCR Copyright (c) 2020.
FAU - Tran, Tuyen Thanh
AU  - Tran TT
AD  - School of Biological Sciences and Technology, Chonnam National University 
      Gwangju, Korea.
FAU - Song, Chin-Hee
AU  - Song CH
AD  - School of Biological Sciences and Technology, Chonnam National University 
      Gwangju, Korea.
FAU - Kim, Kyung-Jin
AU  - Kim KJ
AD  - School of Biological Sciences and Technology, Chonnam National University 
      Gwangju, Korea.
FAU - Lee, Keesook
AU  - Lee K
AD  - School of Biological Sciences and Technology, Chonnam National University 
      Gwangju, Korea.
LA  - eng
PT  - Journal Article
DEP - 20201201
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC7783748
OTO - NOTNLM
OT  - Prostate cancer
OT  - androgen receptor
OT  - androgen-independent activity
OT  - protein degradation
OT  - splice variant
COIS- None.
EDAT- 2021/01/09 06:00
MHDA- 2021/01/09 06:01
PMCR- 2020/12/01
CRDT- 2021/01/08 06:12
PHST- 2020/10/11 00:00 [received]
PHST- 2020/11/12 00:00 [accepted]
PHST- 2021/01/08 06:12 [entrez]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/01/09 06:01 [medline]
PHST- 2020/12/01 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2020 Dec 1;10(12):4607-4623. eCollection 2020.