PMID- 24737574
OWN - NLM
STAT- MEDLINE
DCOM- 20150221
LR  - 20140429
IS  - 1860-7187 (Electronic)
IS  - 1860-7179 (Linking)
VI  - 9
IP  - 5
DP  - 2014 May
TI  - Design, synthesis, and activity evaluation of GK/PPARgamma dual-target-directed 
      ligands as hypoglycemic agents.
PG  - 922-7
LID - 10.1002/cmdc.201400009 [doi]
AB  - Based on the multi-target strategy to treat type 2 diabetes mellitus (T2DM), 
      glucokinase/peroxisome proliferator-activated receptor gamma (GK/PPARgamma) dual-target 
      molecules were constructed by the rational combination of pharmacophores from 
      known GK activators and PPARgamma agonists. A series of dual-target agents were 
      designed and synthesized, and their capacities to induce GK and PPARgamma 
      transcriptional activity were evaluated. Three of these compounds showed 
      particularly high potency toward GK, moderate activity toward PPARgamma, and their 
      structure-activity relationships were preliminarily analyzed. The putative 
      binding modes of one of the most promising compounds were also explored by 
      molecular docking simulations with GK and PPARgamma.
CI  - (c) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Lu, Jianxun
AU  - Lu J
AD  - Capital Normal University, 105 North Xisanhuan Road, Beijing, 100048 (China).
FAU - Lei, Lei
AU  - Lei L
FAU - Huan, Yi
AU  - Huan Y
FAU - Li, Yongqiang
AU  - Li Y
FAU - Zhang, Lijing
AU  - Zhang L
FAU - Shen, Zhufang
AU  - Shen Z
FAU - Hu, Wenxiang
AU  - Hu W
FAU - Feng, Zhiqiang
AU  - Feng Z
LA  - eng
PT  - Journal Article
DEP - 20140415
PL  - Germany
TA  - ChemMedChem
JT  - ChemMedChem
JID - 101259013
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Ligands)
RN  - 0 (PPAR gamma)
RN  - EC 2.7.1.2 (Glucokinase)
SB  - IM
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Dose-Response Relationship, Drug
MH  - *Drug Design
MH  - Glucokinase/*metabolism
MH  - Humans
MH  - Hypoglycemic Agents/*chemical synthesis/chemistry/*pharmacology
MH  - Ligands
MH  - Models, Molecular
MH  - Molecular Structure
MH  - PPAR gamma/*agonists/metabolism
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - PPAR
OT  - activators
OT  - agonists
OT  - dual targeting
OT  - glucokinase
OT  - receptors
EDAT- 2014/04/17 06:00
MHDA- 2015/02/24 06:00
CRDT- 2014/04/17 06:00
PHST- 2014/01/02 00:00 [received]
PHST- 2014/04/17 06:00 [entrez]
PHST- 2014/04/17 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
AID - 10.1002/cmdc.201400009 [doi]
PST - ppublish
SO  - ChemMedChem. 2014 May;9(5):922-7. doi: 10.1002/cmdc.201400009. Epub 2014 Apr 15.