Abstract
Recent studies have shown the potential application of ivermectins in the treatment of alcohol use disorder (AUD). Ivermectin is a positive allosteric modulator (PAM) of P2X4R and this molecule exerts its action in the transmembrane region (known as the TM region) of trimeric channel structure (the pocket formed by Asp331, Met336, Trp46, Trp50, and Tyr42). The aim of this study is to identify FDA drugs with potential PAM properties, by exploring the P2X4Rs from four organisms (Danio rerio, Mus musculus, Rattus norvegicus, and Homo sapiens). The in silico study consists of carrying out the molecular docking of 1656 FDA-approved drugs on the structure of P2X4R, using the commercially available compounds from the ZINC15 database for virtual screening. To strengthen the reliability of the results, two docking protocols were used involving the use of two programs, Autodock 4.2 and Autodock Vina. Nine FDA drugs with potential PAM properties were identified. In addition, eight molecules with potential negative allosteric modulator (NAM) action, and 13 molecules with potential allosteric modulator (AM) action were identified. The FDA drugs identified in this study with PAM, NAM, and AM action, shared in the P2X4Rs of the four organisms...Continue Reading
References
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Nov 24, 2004·Biological Psychiatry·Ting-Kai LiBridget F Grant
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·E Krissinel, K Henrick
Apr 4, 2009·Physiological Reviews·Jürgen Sandkühler
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Jun 6, 2009·Journal of Computational Chemistry·Oleg Trott, Arthur J Olson
Jul 31, 2009·Nature·Toshimitsu KawateEric Gouaux
Nov 3, 2009·Journal of Neurochemistry·Maya PopovaDaryl L Davies
Jun 15, 2010·The Journal of Pharmacology and Experimental Therapeutics·Liana AsatryanDaryl L Davies
Apr 13, 2011·The Journal of Biological Chemistry·Young-Hwan JoEric Boué-Grabot
Dec 14, 2011·Journal of Chemical Information and Modeling·Andrea VolkamerMatthias Rarey
Apr 27, 2012·Nature·Motoyuki Hattori, Eric Gouaux
Sep 26, 2013·Inflammation·Faxin LiLiqing Kou
Jan 24, 2014·The International Journal of Neuropsychopharmacology·Liana AsatryanDaryl L Davies
Dec 1, 2012·International Journal for Parasitology. Drugs and Drug Resistance·Roger PrichardAnne Lespine
Jul 11, 2014·Frontiers in Neuroscience·Kelle M FranklinDaryl L Davies
Nov 27, 2014·World Journal of Biological Chemistry·Alessia Franceschini, Elena Adinolfi
Jan 7, 2015·Journal of Chemical Information and Modeling·Thomas SanderChristian Rufener
Mar 31, 2015·Bioinformatics·Bachir BalechGraziano Pesole
Apr 16, 2015·Nucleic Acids Research·Sebastian SalentinMichael Schroeder
Oct 20, 2015·Journal of Chemical Information and Modeling·Teague Sterling, John J Irwin
Nov 5, 2015·Purinergic Signalling·Lin ChenChao-ying Li
Dec 10, 2015·Molecular Medicine Reports·Hongxia ChenXiuqin Ni
Feb 28, 2016·Advances in Pharmacology·Geoffrey Burnstock
Nov 22, 2016·Biochemical Pharmacology·Aliaa AbdelrahmanChrista E Müller
Dec 3, 2016·Nucleic Acids Research·UNKNOWN The UniProt Consortium
Nov 29, 2017·Biomedical Journal·Jaanus SuurväliSirje Rüütel Boudinot
Mar 4, 2018·Psychopharmacology·Sheraz KhojaDaryl L Davies
May 23, 2018·Nucleic Acids Research·Andrew WaterhouseTorsten Schwede
Jul 6, 2018·EMBO Molecular Medicine·Alazne ZabalaMaría Domercq
Jul 25, 2018·EMBO Molecular Medicine·Francesco Di Virgilio, Alba Clara Sarti
Nov 6, 2018·Purinergic Signalling·Li WangYinli Song
Mar 17, 2019·International Journal of Molecular Sciences·Francisco Reyes-EspinosaGildardo Rivera