Chemogenomics knowledgebased polypharmacology analyses of drug abuse related G-protein coupled receptors and their ligands.
Chemogenomics knowledgebased polypharmacology analyses of drug abuse related G-protein coupled receptors and their ligands.
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基于化学基因组学知识的药物滥用相关 G 蛋白偶联受体及其配体的多药理学分析。
DOI：
10.3389/fphar.2014.00003
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发表时间：
2014
影响因子：
5.6
通讯作者：
Su W
中科院分区：
文献类型：
--
作者：
Xie XQ;Wang L;Liu H;Ouyang Q;Fang C;Su W
药物滥用 (DA) 和成瘾是一种复杂的疾病，被广泛视为神经生物学损伤，遗传和环境因素影响其发展和表现。滥用的物质可以通过与许多蛋白质，特别是 G 蛋白偶联受体 (GPCR) 相互作用，破坏神经元的活动。一些针对中枢神经系统 (CNS) 的药物也可以调节 DA 相关蛋白，例如 GPCR，它可以与受控精神活性物质联合作用并增加副作用。为了充分探索 DA 背后的分子相互作用网络，并用小分子有效调节这些网络中的 GPCR 以进行 DA 治疗，我们建立了药物滥用领域特异性化学基因组学知识库 (DA-KB)，以集中已报告的与 DA 和 CNS 疾病相关的化学基因组学研究信息，以造福于广泛学科的研究人员。然后我们重点分析 GPCR，因为其中许多与 DA 密切相关。还分析了它们在人体组织中的分布，以研究滥用药物引起的副作用。我们进一步实施我们的计算算法/工具来探索多药成瘾中涉及的 DA 靶点、DA 机制和途径，并探索 GPCR 配体的多药理作用。最后，研究了针对 DA 治疗的 GPCR 靶向药物的多药理学效应，并可利用这种效应来开发用于 DA 干预的多药效团药物。化学基因组学数据库和分析工具将帮助我们更好地了解药物滥用的机制，并有助于设计用于DA系统药物治疗的新药物。
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.
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影响因子：
5.2
作者：
Lee AM;Messing RO
通讯作者：
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