eprintid: 24872
rev_number: 25
userid: 4439
dir: disk0/00/02/48/72
datestamp: 2015-05-05 15:49:46
lastmod: 2021-03-10 06:19:12
status_changed: 2015-05-05 15:49:46
type: article
metadata_visibility: show
contact_email: xix15@pitt.edu
item_issues_count: 0
eprint_status: archive
creators_name: Xie, XQ
creators_name: Wang, L
creators_name: Liu, H
creators_name: Ouyang, Q
creators_name: Fang, C
creators_name: Su, W
creators_email: Sean.Xie@pitt.edu
creators_email: LIW30@pitt.edu
creators_email: 
creators_email: 
creators_email: chf42@pitt.edu
creators_email: 
creators_id: XIX15
creators_id: LIW30
creators_id: 
creators_id: 
creators_id: CHF42
creators_id: 
title: Chemogenomics knowledgebased polypharmacology analyses of drug abuse related G-protein coupled receptors and their ligands
ispublished: pub
divisions: sch_as_chemistry
divisions: sch_med_Computational_Systems_Biology
divisions: sch_phm_pharmaceuticalsciences
full_text_status: public
abstract: Drug abuse (DA) and addiction is a complex illness, broadly viewed as a neurobiological impairment with genetic and environmental factors that influence its development and manifestation. Abused substances can disrupt the activity of neurons by interacting with many proteins, particularly G-protein coupled receptors (GPCRs). A few medicines that target the central nervous system (CNS) can also modulate DA related proteins, such as GPCRs, which can act in conjunction with the controlled psychoactive substance(s) and increase side effects. To fully explore the molecular interaction networks that underlie DA and to effectively modulate the GPCRs in these networks with small molecules for DA treatment, we built a drug-abuse domain specific chemogenomics knowledgebase (DA-KB) to centralize the reported chemogenomics research information related to DA and CNS disorders in an effort to benefit researchers across a broad range of disciplines. We then focus on the analysis of GPCRs as many of them are closely related with DA. Their distribution in human tissues was also analyzed for the study of side effects caused by abused drugs. We further implement our computational algorithms/tools to explore DA targets, DA mechanisms and pathways involved in polydrug addiction and to explore polypharmacological effects of the GPCR ligands. Finally, the polypharmacology effects of GPCRs-targeted medicines for DA treatment were investigated and such effects can be exploited for the development of drugs with polypharmacophore for DA intervention. The chemogenomics database and the analysis tools will help us better understand the mechanism of drugs abuse and facilitate to design new medications for system pharmacotherapy of DA. © 2014 Xie, Wang, Liu, Ouyang, Fang and Su.
date: 2014-01-01
date_type: published
publication: Frontiers in Pharmacology
volume: 5 FEB
refereed: TRUE
centers: cen_other_drugdiscoveryinst
id_number: 10.3389/fphar.2014.00003
citation:   Xie, XQ and Wang, L and Liu, H and Ouyang, Q and Fang, C and Su, W  (2014) Chemogenomics knowledgebased polypharmacology analyses of drug abuse related G-protein coupled receptors and their ligands.  Frontiers in Pharmacology, 5 FEB.       
document_url: http://d-scholarship-dev.library.pitt.edu/24872/1/fphar-05-00003.pdf
document_url: http://d-scholarship-dev.library.pitt.edu/24872/4/licence.txt