对实验室代号为 SV-1010 的吲哚衍生物和其他非甾体抗炎药的候选分子进行化学蛋白组学分析

Q3 Pharmacology, Toxicology and Pharmaceutics
P. Galenko-Yaroshevsky, I. Torshin, A. N. Gromov, I. A. Reyer, O. Gromova, Tereza R. Glechyan, Konstantin F. Suzdalev, Andrey V. Zadorozhniy, A. Zelenskaya
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引用次数: 0

摘要

导言:为了对疼痛进行有效而安全的药物治疗,必须评估非甾体抗炎药(NSAIDs)的作用机制和作用范围,包括其对蛋白体的影响、中枢效应以及止痛和抗炎作用。该研究的目的是评估吲哚衍生物 SV-1010 这一有希望的候选分子与知名非甾体抗炎药之间的复杂差异:通过化学图谱拓扑分析,对 SV-1010 和非甾体抗炎药双氯芬酸、尼美舒利和酮咯酸对大鼠蛋白质组的药理作用进行化学蛋白质组学调制:结果发现,所研究分子对大鼠蛋白质组中 820 种蛋白质的影响存在明显差异。SV-1010 能抑制多巴胺 D1 和 D2 型受体,同时刺激新纹状体中多巴胺的释放(EC50 = 27 nM),但抑制程度低于其他分子。与其他分子相比,SV-1010 能在更大程度上抑制 GABA 传达子(EC50 = 65 nM)和 NMDA 受体 Grin1/Grin2b(IC50 175 nM)。SV-1010 能激活大麻素 CB2 受体,抑制白三烯生物合成酶、促炎趋化因子和白三烯的 CC 受体:SV-1010的化学反应组学和化学蛋白组学分析表明,它可以通过多巴胺能和GABA神经传递以及其他抗炎机制发挥潜在的中枢效应,这有助于增强镇痛效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs
Introduction: For effective and safe pharmacotherapy of pain, it is important to evaluate the mechanisms and spectrum of action of non-steroidal anti-inflammatory drugs (NSAIDs), including their effect on the proteom, central effect, as well as pain relieving and anti-inflammatory effects. The aim of the study was to evaluate the complex of differences between the promising candidate-molecule of indole derivative SV-1010 and the well-known NSAIDs. Materials and Methods: Chemoproteomic moduling of pharmacological effects of SV-1010 and NSAID diclofenac, nimesulide and ketorolac on the rat proteom by means of topological analysis of chemographs. Results: The significant differences in the effects of the studied molecules were found for 820 proteins of the rat proteom. SV-1010, to a lesser degree than the other molecules, can inhibit dopamine D1- and D2-type receptors and, at the same time, stimulate the release of dopamine in the neostriatum (EC50 = 27 nM). SV-1010, to a greater extent than the other molecules, can inhibit the GABA conveyor (EC50 = 65 nM) and the NMDA receptors Grin1/Grin2b (IC50 175 nM). SV-1010 can activate Cannabinoid CB2 receptors, inhibit enzymes of leukotriene biosynthesis, CC receptors of pro-inflammatory chemokines and leukotrienes. Conclusion: The chemoreactomic and chemoproteomic profiling of SV-1010 indicated its potential central effect through dopaminergic and GABA-neurotransmission and additional anti-inflammatory mechanisms, which can help increase pain-relieving effects.
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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