PMID- 28109945
OWN - NLM
STAT- MEDLINE
DCOM- 20170221
LR  - 20231213
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 127
DP  - 2017 Feb 15
TI  - Discovery of a series of N-(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as 
      PI3K/mTOR dual inhibitors.
PG  - 509-520
LID - S0223-5234(17)30024-7 [pii]
LID - 10.1016/j.ejmech.2017.01.016 [doi]
AB  - Recently, the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin 
      (mTOR) have been considered as promising targets for the treatment of cancer. 
      Herein, we synthesized a series of 
      N-(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as novel PI3K/mTOR dual 
      inhibitors for cancer therapy. In the biological evaluation, compound 17e was 
      identified as a potent PI3K/mTOR dual inhibitor, which significantly inhibit 
      Class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level. 
      Moreover, 17e display high potency against PC-3 cells (IC(50) = 80 nM) in the 
      anti-proliferative assay, and showed acceptable pharmacokinetic properties 
      in vivo.
CI  - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved.
FAU - Zhang, Jiankang
AU  - Zhang J
AD  - Department of Pharmaceutical Preparation, Hangzhou Xixi Hospital, Hangzhou 
      310023, China.
FAU - Lv, Xiaoqing
AU  - Lv X
AD  - College of Medicine, Jiaxing University, Jiaxing 314001, China. Electronic 
      address: lxqd1@126.com.
FAU - Ma, Xiaodong
AU  - Ma X
AD  - Department of Medicinal Chemistry, School of Pharmacy, Anhui University of 
      Chinese Medicine, Hefei 230031, China.
FAU - Hu, Yongzhou
AU  - Hu Y
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
LA  - eng
PT  - Journal Article
DEP - 20170111
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Chemistry Techniques, Synthetic
MH  - *Drug Design
MH  - Humans
MH  - Male
MH  - Mice
MH  - Molecular Docking Simulation
MH  - Phosphatidylinositol 3-Kinases/chemistry/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Conformation
MH  - Protein Kinase Inhibitors/*chemical 
      synthesis/metabolism/pharmacokinetics/*pharmacology
MH  - Sulfonamides/*chemical synthesis/metabolism/pharmacokinetics/*pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Xenograft Model Antitumor Assays
MH  - Benzenesulfonamides
OTO - NOTNLM
OT  - Cancer
OT  - Inhibitor
OT  - PI3K
OT  - mTOR
EDAT- 2017/01/23 06:00
MHDA- 2017/02/22 06:00
CRDT- 2017/01/23 06:00
PHST- 2016/11/18 00:00 [received]
PHST- 2017/01/09 00:00 [revised]
PHST- 2017/01/10 00:00 [accepted]
PHST- 2017/01/23 06:00 [pubmed]
PHST- 2017/02/22 06:00 [medline]
PHST- 2017/01/23 06:00 [entrez]
AID - S0223-5234(17)30024-7 [pii]
AID - 10.1016/j.ejmech.2017.01.016 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2017 Feb 15;127:509-520. doi: 10.1016/j.ejmech.2017.01.016. Epub 
      2017 Jan 11.