Deciphering Imidazoline Off-Targets by Fishing in the Class A of GPCR field

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Djikic , T , Vucicevic , J , Laurila , J , Radi , M , Veljkovic , N , Xhaard , H & Nikolic , K M 2020 , ' Deciphering Imidazoline Off-Targets by Fishing in the Class A of GPCR field ' , Molecular informatics , vol. 39 , no. 7 , 1900165 . https://doi.org/10.1002/minf.201900165

Titel: Deciphering Imidazoline Off-Targets by Fishing in the Class A of GPCR field
Författare: Djikic, Teodora; Vucicevic, Jelica; Laurila, Jonne; Radi, Marco; Veljkovic, Nevena; Xhaard, Henri; Nikolic, Katarina M.
Upphovmannens organisation: Division of Pharmaceutical Chemistry and Technology
Division of Pharmaceutical Biosciences
Drug Research Program
Pharmaceutical Design and Discovery group
Computational Adme
Datum: 2020-07
Språk: eng
Sidantal: 12
Tillhör serie: Molecular informatics
ISSN: 1868-1743
DOI: https://doi.org/10.1002/minf.201900165
Permanenta länken (URI): http://hdl.handle.net/10138/326822
Abstrakt: Based on the finding that a central antihypertensive agent with high affinity for I1-type imidazoline receptors ? rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α-adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α-adrenoceptors belong to the rhodopsin-like class A of G-protein-coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class. Therefore, to investigate possible off-target effects of imidazoline ligands we have prepared a reverse docking protocol on class A GPCRs, using imidazoline ligands and their decoys. To verify our in silico results, three ligands with high scores and three ligands with low scores were tested for antagonistic activity on α2- adrenoceptors.
Subject: ALPHA(2)-ADRENOCEPTORS
BINDING-AFFINITY
CRYSTAL-STRUCTURE
GPCRs
I-1-IMIDAZOLINE RECEPTOR
IDENTIFICATION
LIGAND
MODELS
PROTEIN
REVERSE DOCKING
SITES
imidazolines
off-target
reverse docking
target fishing
317 Pharmacy
318 Medical biotechnology
1182 Biochemistry, cell and molecular biology
Referentgranskad: Ja
Licens: unspecified
Användningsbegränsning: openAccess
Parallelpublicerad version: acceptedVersion


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