PMID- 29681156
OWN - NLM
STAT- MEDLINE
DCOM- 20190603
LR  - 20190603
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 61
IP  - 10
DP  - 2018 May 24
TI  - Fluorescent-Labeled Selective Adenosine A(2B) Receptor Antagonist Enables 
      Competition Binding Assay by Flow Cytometry.
PG  - 4301-4316
LID - 10.1021/acs.jmedchem.7b01627 [doi]
AB  - Fluorescent ligands represent powerful tools for biological studies and are 
      considered attractive alternatives to radioligands. In this study, we developed 
      fluorescent antagonists for A(2B) adenosine receptors (A(2B)ARs), which are 
      targeted by antiasthmatic xanthines and were proposed as novel targets in 
      immuno-oncology. Our approach was to merge a small borondipyrromethene (BODIPY) 
      derivative with the pharmacophore of 8-substituted xanthine derivatives. On the 
      basis of the design, synthesis, and evaluation of model compounds, several 
      fluorescent ligands were synthesized. Compound 29 (PSB-12105), which displayed 
      high affinity for human, rat, and mouse A(2B)ARs ( K(i) = 0.2-2 nM) and high 
      selectivity for this AR subtype, was selected for further studies. A homology 
      model of the human A(2B)AR was generated, and docking studies were performed. 
      Moreover, 29 allowed us to establish a homogeneous receptor-ligand binding assay 
      using flow cytometry. These compounds constitute the first potent, selective 
      fluorescent A(2B)AR ligands and are anticipated to be useful for a variety of 
      applications.
FAU - Kose, Meryem
AU  - Kose M
AD  - PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I , 
      University of Bonn , An der Immenburg 4 , D-53121 Bonn , Germany.
FAU - Gollos, Sabrina
AU  - Gollos S
AD  - PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I , 
      University of Bonn , An der Immenburg 4 , D-53121 Bonn , Germany.
FAU - Karcz, Tadeusz
AU  - Karcz T
AD  - Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy , 
      Jagiellonian University Medical College , Medyczna 9 , 30-688 Krakow , Poland.
FAU - Fiene, Amelie
AU  - Fiene A
AD  - PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I , 
      University of Bonn , An der Immenburg 4 , D-53121 Bonn , Germany.
FAU - Heisig, Fabian
AU  - Heisig F
AD  - PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I , 
      University of Bonn , An der Immenburg 4 , D-53121 Bonn , Germany.
FAU - Behrenswerth, Andrea
AU  - Behrenswerth A
AD  - PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I , 
      University of Bonn , An der Immenburg 4 , D-53121 Bonn , Germany.
FAU - Kiec-Kononowicz, Katarzyna
AU  - Kiec-Kononowicz K
AD  - Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy , 
      Jagiellonian University Medical College , Medyczna 9 , 30-688 Krakow , Poland.
FAU - Namasivayam, Vigneshwaran
AU  - Namasivayam V
AD  - PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I , 
      University of Bonn , An der Immenburg 4 , D-53121 Bonn , Germany.
FAU - Muller, Christa E
AU  - Muller CE
AUID- ORCID: 0000-0002-0013-6624
AD  - PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I , 
      University of Bonn , An der Immenburg 4 , D-53121 Bonn , Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180515
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Adenosine A2 Receptor Antagonists)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Receptor, Adenosine A2B)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Adenosine A2 Receptor Antagonists/*pharmacology
MH  - Animals
MH  - Binding, Competitive
MH  - CHO Cells
MH  - Cell Proliferation
MH  - Cricetinae
MH  - Cricetulus
MH  - Cyclic AMP/metabolism
MH  - Flow Cytometry/*methods
MH  - Fluorescent Dyes/*chemistry
MH  - Humans
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Protein Binding
MH  - Protein Conformation
MH  - Radioligand Assay
MH  - Rats
MH  - Receptor, Adenosine A2B/*chemistry
EDAT- 2018/04/24 06:00
MHDA- 2019/06/04 06:00
CRDT- 2018/04/24 06:00
PHST- 2018/04/24 06:00 [pubmed]
PHST- 2019/06/04 06:00 [medline]
PHST- 2018/04/24 06:00 [entrez]
AID - 10.1021/acs.jmedchem.7b01627 [doi]
PST - ppublish
SO  - J Med Chem. 2018 May 24;61(10):4301-4316. doi: 10.1021/acs.jmedchem.7b01627. Epub 
      2018 May 15.