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
Title: | Deciphering Imidazoline Off-Targets by Fishing in the Class A of GPCR field |
Author: | Djikic, Teodora; Vucicevic, Jelica; Laurila, Jonne; Radi, Marco; Veljkovic, Nevena; Xhaard, Henri; Nikolic, Katarina M. |
Contributor organization: | Division of Pharmaceutical Chemistry and Technology Division of Pharmaceutical Biosciences Drug Research Program Pharmaceutical Design and Discovery group Computational Adme |
Date: | 2020-07 |
Language: | eng |
Number of pages: | 12 |
Belongs to series: | Molecular informatics |
ISSN: | 1868-1743 |
DOI: | https://doi.org/10.1002/minf.201900165 |
URI: | http://hdl.handle.net/10138/326822 |
Abstract: | 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 |
Peer reviewed: | Yes |
Rights: | unspecified |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
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