PMID- 24943256
OWN - NLM
STAT- MEDLINE
DCOM- 20150626
LR  - 20211021
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 171
IP  - 21
DP  - 2014 Nov
TI  - (4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a novel 
      inhibitor of autophagy.
PG  - 4970-80
LID - 10.1111/bph.12821 [doi]
AB  - BACKGROUND AND PURPOSE: Autophagy is an important intracellular degradation 
      system, which is related to various diseases. In preliminary experiments we found 
      that D4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline (DMH1) 
      inhibited autophagy responses. However DMH1 also inhibits the signalling pathway 
      activated by bone morphogenetic protein-4 (BMP4). The aim of the present study 
      was to elucidate the inhibitory effects of DMH1 on autophagy and the underlying 
      mechanisms. EXPERIMENTAL APPROACH: The effects of DMH1 on autophagy responses 
      were evaluated in cultures of different cell types and with different stimuli to 
      induce autophagy, using Western blots, transmission electron microscopy and 
      fluorescent microscopy. KEY RESULTS: DMH1 inhibited starvation-induced autophagy 
      in cardiomyocytes, HeLa and MCF-7 cells, without involving the signalling pathway 
      of BMP4. DMH1 inhibited aminoimidazole carboxamide ribonucleotide (AICAR)- and 
      rapamycin-induced autophagy in HeLa and MCF-7 cells. DMH1 reversed starvation- 
      and AICAR-induced inhibition of Akt, mammalian target of rapamycin (mTOR) and 
      p70S6 kinase (S6K), and reversed rapamycin-induced inhibition of mTOR and S6K. 
      DMH1 reversed starvation-induced decrease of the phosphorylated form of glycogen 
      synthase kinase-3 in MCF-7 and HT29 cells. Activation of Akt and inhibition of 
      autophagy induced by DMH1 were antagonized by an Akt specific inhibitor or by 
      small interfering RNA for Akt in HeLa cells. CONCLUSION AND IMPLICATIONS: DMH1 
      inhibited cellular autophagy responses in a range of cell types and the 
      underlying mechanisms include activation of the Akt pathway.
CI  - (c) 2014 The British Pharmacological Society.
FAU - Sheng, Yue
AU  - Sheng Y
AD  - Department of Pharmacology (the State-Province Key Laboratories of 
      Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, 
      Ministry of Education), Harbin Medical University, Harbin, Heilongjiang, China.
FAU - Sun, Bo
AU  - Sun B
FAU - Guo, Wen-Ting
AU  - Guo WT
FAU - Liu, Xiao
AU  - Liu X
FAU - Wang, Yu-Chun
AU  - Wang YC
FAU - Xie, Xin
AU  - Xie X
FAU - Xiao, Xiao-Lin
AU  - Xiao XL
FAU - Li, Na
AU  - Li N
FAU - Dong, De-Li
AU  - Dong DL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140905
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (DMH1 compound)
RN  - 0 (Pyrazoles)
RN  - 0 (Quinolines)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects/physiology
MH  - Cells, Cultured
MH  - HT29 Cells
MH  - HeLa Cells
MH  - Humans
MH  - MCF-7 Cells
MH  - Myocytes, Cardiac/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyrazoles/*pharmacology
MH  - Quinolines/*pharmacology
MH  - Rats, Wistar
PMC - PMC4294118
EDAT- 2014/06/20 06:00
MHDA- 2015/06/27 06:00
PMCR- 2015/11/01
CRDT- 2014/06/20 06:00
PHST- 2014/01/07 00:00 [received]
PHST- 2014/06/06 00:00 [revised]
PHST- 2014/06/09 00:00 [accepted]
PHST- 2014/06/20 06:00 [entrez]
PHST- 2014/06/20 06:00 [pubmed]
PHST- 2015/06/27 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - 10.1111/bph.12821 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2014 Nov;171(21):4970-80. doi: 10.1111/bph.12821. Epub 2014 Sep 
      5.