TY - JOUR
T1 - In Silico Analysis of FDA Drugs as P2X4 Modulators for the Treatment of Alcohol Use Disorder
AU - Reyes-Espinosa, Francisco
AU - Nieto-Pescador, María G.
AU - Bocanegra-García, Virgilio
AU - Lozano-Guzmán, Eduardo
AU - Rivera, Gildardo
N1 - Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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, can provide a guideline to proceed with research concerning new drugs for the study and treatment of AUD.
AB - 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, can provide a guideline to proceed with research concerning new drugs for the study and treatment of AUD.
KW - P2X4 receptor
KW - allosteric modulators
KW - drug repositioning
KW - molecular docking
KW - molecular modeling
KW - virtual screening
UR - http://www.scopus.com/inward/record.url?scp=85086163503&partnerID=8YFLogxK
U2 - 10.1002/minf.201900111
DO - 10.1002/minf.201900111
M3 - Artículo
C2 - 32511896
SN - 1868-1743
VL - 39
JO - Molecular Informatics
JF - Molecular Informatics
IS - 9
M1 - 1900111
ER -