Display options
Cite
Novikov FN, Panova MV, Titov IY, et al. Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis. Sci Rep. 2021;11(1):23120doi: 10.1038/s41598-021-02568-6.
Novikov, F. N., Panova, M. V., Titov, I. Y., Stroylov, V. S., Stroganov, O. V., & Chilov, G. G. (2021). Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis. Scientific reports, 11(1), 23120. https://doi.org/10.1038/s41598-021-02568-6
Novikov, F N, et al. "Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis." Scientific reports vol. 11,1 (2021): 23120. doi: https://doi.org/10.1038/s41598-021-02568-6
Novikov FN, Panova MV, Titov IY, Stroylov VS, Stroganov OV, Chilov GG. Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis. Sci Rep. 2021 Nov 30;11(1):23120. doi: 10.1038/s41598-021-02568-6. PMID: 34848799; PMCID: PMC8632988.
Copy Download .nbib Format: NLM
Share it on

Sci Rep. 2021 Nov 30;11(1):23120. doi: 10.1038/s41598-021-02568-6.

Inhibition of SYK and cSrc kinases can protect bone and cartilage in preclinical models of osteoarthritis and rheumatoid arthritis.

Scientific reports

F N Novikov, M V Panova, I Y Titov, V S Stroylov, O V Stroganov, G G Chilov

Affiliations

  1. Molecular Technologies, LLC, Moscow, Russian Federation.
  2. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, Moscow, Russian Federation, 119991.
  3. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, Moscow, Russian Federation, 119991. [email protected].
  4. National Research University Higher School of Economics (HSE), 20 Myasnitskaya Street, Moscow, Russian Federation, 101000. [email protected].
  5. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, Moscow, Russian Federation, 119991. [email protected].

PMID: 34848799 PMCID: PMC8632988 DOI: 10.1038/s41598-021-02568-6

Abstract

The pathophysiology of osteoarthritis (OA) includes the destruction of subchondral bone tissue and inflammation of the synovium. Thus, an effective disease-modifying treatment should act on both of these pathogenetic components. It is known that cSrc kinase is involved in bone and cartilage remodeling, and SYK kinase is associated with the inflammatory component. Thus the aim of this study was to characterize the mechanism of action and efficacy of a small molecule multikinase inhibitor MT-SYK-03 targeting SYK and cSrc kinases among others in different in vitro and in vivo arthritis models. The selectivity of MT-SYK-03 kinase inhibition was assayed on a panel of 341 kinases. The compound was evaluated in a set of in vitro models of OA and in vivo OA and RA models: surgically-induced arthritis (SIA), monosodium iodoacetate-induced arthritis (MIA), collagen-induced arthritis (CIA), adjuvant-induced arthritis (AIA). MT-SYK-03 inhibited cSrc and SYK with IC

© 2021. The Author(s).

References

  1. Arthritis Rheumatol. 2014 May;66(5):1247-55 - PubMed
  2. J Biol Chem. 2013 Mar 15;288(11):7430-7437 - PubMed
  3. Int J Clin Exp Med. 2015 Jan 15;8(1):1027-34 - PubMed
  4. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6158-63 - PubMed
  5. Toxicol Pathol. 2003 Nov-Dec;31(6):619-24 - PubMed
  6. J Orthop Translat. 2019 Sep 27;22:50-57 - PubMed
  7. Osteoarthritis Cartilage. 2010 Oct;18 Suppl 3:S24-34 - PubMed
  8. Acta Naturae. 2009 Oct;1(3):84-8 - PubMed
  9. PLoS One. 2020 Apr 24;15(4):e0231501 - PubMed
  10. Nucleic Acids Res. 2002 May 1;30(9):e36 - PubMed
  11. Clin Immunol. 2007 Sep;124(3):244-57 - PubMed
  12. Rheumatology (Oxford). 2013 May;52(5):888-92 - PubMed
  13. Biomed Res Int. 2020 Apr 6;2020:5720360 - PubMed
  14. J Exp Med. 2000 May 1;191(9):1611-6 - PubMed
  15. Osteoarthritis Cartilage. 2003 Nov;11(11):821-30 - PubMed
  16. Curr Rheumatol Rep. 2013 Nov;15(11):375 - PubMed
  17. Mediators Inflamm. 2020 Mar 3;2020:8293921 - PubMed
  18. Trends Pharmacol Sci. 2014 Aug;35(8):414-22 - PubMed
  19. J Rheumatol. 2014 Nov;41(11):2120-8 - PubMed
  20. J Biol Chem. 2003 May 9;278(19):16761-9 - PubMed
  21. Mol Biol Rep. 2012 Nov;39(11):9965-70 - PubMed
  22. Curr Pharm Des. 2010;16(27):3015-27 - PubMed
  23. Arthritis. 2012;2012:741582 - PubMed
  24. J Clin Med. 2019 Aug 29;8(9): - PubMed
  25. Mod Rheumatol. 2006;16(2):68-74 - PubMed
  26. Expert Opin Emerg Drugs. 2018 Dec;23(4):331-347 - PubMed
  27. Curr Opin Rheumatol. 2010 Mar;22(2):139-43 - PubMed
  28. Cell Mol Life Sci. 2014 Mar;71(6):1081-96 - PubMed
  29. J Oral Maxillofac Surg. 1997 Jan;55(1):20-7; discussion 27-8 - PubMed
  30. Osteoarthritis Cartilage. 2002 Dec;10(12):961-7 - PubMed
  31. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008 - PubMed
  32. Am J Hematol. 2018 Jul;93(7):921-930 - PubMed
  33. Biochem J. 2013 Apr 15;451(2):313-28 - PubMed
  34. Calcif Tissue Int. 2018 Feb;102(2):227-250 - PubMed
  35. Nat Rev Rheumatol. 2012 Nov;8(11):665-73 - PubMed
  36. Trans Am Clin Climatol Assoc. 2013;124:16-25 - PubMed
  37. J Bone Miner Res. 2010 Aug;25(8):1759-70 - PubMed
  38. Trials. 2015 Mar 04;16:77 - PubMed
  39. Curr Rheumatol Rep. 2017 Aug;19(8):45 - PubMed
  40. Autoimmunity. 2010 Feb;43(1):48-55 - PubMed
  41. Clin Geriatr Med. 2010 Aug;26(3):355-69 - PubMed
  42. J Pharmacol Exp Ther. 2012 Feb;340(2):350-9 - PubMed
  43. Immunotargets Ther. 2020 Mar 09;9:43-56 - PubMed
  44. J Bone Miner Res. 2020 Mar;35(3):505-515 - PubMed
  45. Arthritis Res Ther. 2018 May 30;20(1):103 - PubMed
  46. Curr Pharm Des. 2002;8(23):2049-75 - PubMed
  47. Connect Tissue Res. 2016 Jul;57(4):245-61 - PubMed
  48. Pharmacol Res Perspect. 2015 Oct;3(5):e00175 - PubMed
  49. Clin Cases Miner Bone Metab. 2015 Jan-Apr;12(1):69-74 - PubMed
  50. Osteoarthritis Cartilage. 2016 Dec;24(12):2013-2021 - PubMed
  51. Curr Opin Rheumatol. 2009 Sep;21(5):513-9 - PubMed
  52. Pain. 2004 Nov;112(1-2):83-93 - PubMed
  53. Nat Rev Rheumatol. 2015 Jan;11(1):35-44 - PubMed
  54. Osteoarthritis Cartilage. 2002 Oct;10(10):785-91 - PubMed
  55. Nan Fang Yi Ke Da Xue Xue Bao. 2019 Jun 30;39(6):747-750 - PubMed
  56. Osteoarthritis Cartilage. 2006 Oct;14(10):1041-8 - PubMed
  57. Bone. 2016 Feb;83:190-196 - PubMed
  58. Osteoarthritis Cartilage. 2004 Jan;12(1):38-45 - PubMed
  59. Mediators Inflamm. 2014;2014:270302 - PubMed
  60. Sci Rep. 2016 Feb 16;6:21262 - PubMed
  61. Anesth Pain Med. 2019 Apr 27;9(3):e89990 - PubMed
  62. Curr Osteoporos Rep. 2017 Dec;15(6):593-600 - PubMed
  63. DNA Repair (Amst). 2017 Mar;51:14-19 - PubMed

Publication Types