PMID- 26882208
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20180226
IS  - 1549-960X (Electronic)
IS  - 1549-9596 (Linking)
VI  - 56
IP  - 4
DP  - 2016 Apr 25
TI  - Discovery of Potent Soluble Epoxide Hydrolase (sEH) Inhibitors by 
      Pharmacophore-Based Virtual Screening.
PG  - 747-62
LID - 10.1021/acs.jcim.5b00592 [doi]
AB  - There is an increasing interest in the development of soluble epoxide hydrolase 
      (sEH) inhibitors, which block the degradation of endogenous anti-inflammatory 
      epoxyeicosatrienoic acids. Within this study, a set of pharmacophore models for 
      sEH inhibitors was developed. The Specs database was virtually screened and a 
      cell-free sEH activity assay was used for the biological investigation of virtual 
      hits. In total, out of 48 tested compounds, 19 were sEH inhibitors with IC50 < 10 
      muM, representing a prospective true positive hit rate of 40%. Six of these 
      compounds displayed IC50 values in the low nanomolar range. The most potent 
      compound 21, a urea derivative, inhibited sEH with an IC50 = 4.2 nM. The applied 
      approach also enabled the identification of diverse chemical scaffolds, e.g. the 
      pyrimidinone derivative 29 (IC50 = 277 nM). The generated pharmacophore model set 
      therefore represents a valuable tool for the selection of compounds for 
      biological testing.
FAU - Waltenberger, Birgit
AU  - Waltenberger B
AD  - Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences 
      Innsbruck (CMBI), University of Innsbruck , Innrain 80-82, A-6020 Innsbruck, 
      Austria.
FAU - Garscha, Ulrike
AU  - Garscha U
AD  - Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of 
      Jena , Philosophenweg 14, D-07743 Jena, Germany.
FAU - Temml, Veronika
AU  - Temml V
AD  - Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences 
      Innsbruck (CMBI), University of Innsbruck , Innrain 80-82, A-6020 Innsbruck, 
      Austria.
FAU - Liers, Josephine
AU  - Liers J
AD  - Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of 
      Jena , Philosophenweg 14, D-07743 Jena, Germany.
FAU - Werz, Oliver
AU  - Werz O
AD  - Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of 
      Jena , Philosophenweg 14, D-07743 Jena, Germany.
FAU - Schuster, Daniela
AU  - Schuster D
FAU - Stuppner, Hermann
AU  - Stuppner H
AD  - Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences 
      Innsbruck (CMBI), University of Innsbruck , Innrain 80-82, A-6020 Innsbruck, 
      Austria.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160404
PL  - United States
TA  - J Chem Inf Model
JT  - Journal of chemical information and modeling
JID - 101230060
RN  - 0 (Enzyme Inhibitors)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Catalytic Domain
MH  - Drug Evaluation, Preclinical/*methods
MH  - Enzyme Inhibitors/*chemistry/*pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors/*chemistry
MH  - Humans
MH  - Models, Molecular
MH  - Solubility
MH  - Structure-Activity Relationship
MH  - User-Computer Interface
EDAT- 2016/02/18 06:00
MHDA- 2017/08/02 06:00
CRDT- 2016/02/17 06:00
PHST- 2016/02/17 06:00 [entrez]
PHST- 2016/02/18 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
AID - 10.1021/acs.jcim.5b00592 [doi]
PST - ppublish
SO  - J Chem Inf Model. 2016 Apr 25;56(4):747-62. doi: 10.1021/acs.jcim.5b00592. Epub 
      2016 Apr 4.