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 o...
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| Format: | Article |
| Language: | English |
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Belgorod National Research University
2024-07-01
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| Series: | Research Results in Pharmacology |
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| Online Access: | https://rrpharmacology.ru/index.php/journal/article/view/497 |
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| author | Pavel A. Galenko-Yaroshevsky Ivan Yu. Torshin Andrey N. Gromov Ivan A. Reyer Olga A. Gromova Tereza R. Glechyan Konstantin F. Suzdalev Andrey V. Zadorozhniy Anait V. Zelenskaya |
| author_facet | Pavel A. Galenko-Yaroshevsky Ivan Yu. Torshin Andrey N. Gromov Ivan A. Reyer Olga A. Gromova Tereza R. Glechyan Konstantin F. Suzdalev Andrey V. Zadorozhniy Anait V. Zelenskaya |
| author_sort | Pavel A. Galenko-Yaroshevsky |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6acd4504926d46eb93fd505f155ea979 |
| institution | Kabale University |
| issn | 2658-381X |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj-art-6acd4504926d46eb93fd505f155ea9792025-01-08T12:11:24ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2024-07-011031910.18413/rrpharmacology.10.497Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugsPavel A. Galenko-Yaroshevsky0https://orcid.org/0000-0003-3190-1437Ivan Yu. Torshin1https://orcid.org/0000-0002-2659-7998Andrey N. Gromov2https://orcid.org/0000-0001-7507-191XIvan A. Reyer3https://orcid.org/0000-0002-7928-053XOlga A. Gromova4https://orcid.org/0000-0002-7663-710XTereza R. Glechyan5https://orcid.org/0009-0002-4983-2433Konstantin F. Suzdalev6https://orcid.org/0000-0003-4879-0577Andrey V. Zadorozhniy7https://orcid.org/0000-0001-9552-8542Anait V. Zelenskaya8https://orcid.org/0000-0001-9512-2526Kuban State Medical UniversityFederal Research Center “Informatics and Management” of the Russian Academy of SciencesFederal Research Center “Informatics and Management” of the Russian Academy of SciencesFederal Research Center “Informatics and Management” of the Russian Academy of SciencesFederal Research Center “Informatics and Management” of the Russian Academy of SciencesKuban State Medical UniversitySouthern Federal UniversityRostov State Medical UniversityKuban State Medical UniversityIntroduction: 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.https://rrpharmacology.ru/index.php/journal/article/view/497diclofenacketorolacmachine learningnimesulidechemoinformaticsindole derivative sv-1010 |
| spellingShingle | Pavel A. Galenko-Yaroshevsky Ivan Yu. Torshin Andrey N. Gromov Ivan A. Reyer Olga A. Gromova Tereza R. Glechyan Konstantin F. Suzdalev Andrey V. Zadorozhniy Anait V. Zelenskaya Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs Research Results in Pharmacology diclofenac ketorolac machine learning nimesulide chemoinformatics indole derivative sv-1010 |
| title | Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs |
| title_full | Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs |
| title_fullStr | Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs |
| title_full_unstemmed | Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs |
| title_short | Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs |
| title_sort | chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code sv 1010 and other non steroidal anti inflammatory drugs |
| topic | diclofenac ketorolac machine learning nimesulide chemoinformatics indole derivative sv-1010 |
| url | https://rrpharmacology.ru/index.php/journal/article/view/497 |
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