Mechanism of action

Cyendiv® is a multitargeted tyrosine kinase inhibitor with antifibrotic and anti-inflammatory effects that inhibit key pathways leading to pulmonary fibrosis1,3–7
Cyendiv® is a non-immunosuppressant and the only approved treatment option for patients with SSc-ILD1,8

CYENDIV targets key receptor tyrosine kinases PDGFR, FGFR and VEGFR

Adapted from Wollin L et al. Eur Respir J.2015;45:1434-1445.

Cyendiv® binds intracellularly to key tyrosine kinases that have been implicated in the pathogenesis of pulmonary fibrosis (in interstitial lung diseases (ILDs)).1,4-7

Cyendiv® targets key receptors, platelet-derived growth factor receptor (PDGFR) α and ß, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and colony-stimulating factor 1 receptor (CSF1R), associated with pathogenic processes in pulmonary fibrosis to reduce:1,4-7

  •   Fibroblast proliferation  
  •   Migration  
  •   Fibroblast-to-myofibroblast transformation  
  •   Activation of macrophages  

In addition, Cyendiv® inhibits lymphocyte-specific tyrosine-protein kinase (Lck), involved in the activation of T cells, reducing the activation of fibroblasts and the synthesis and secretion of extracellular matrix (ECM).1,6,7

While ILDs differ, common pathogenic pathways to pulmonary fibrosis are shared9

Repeated injury and deterioration of repair mechanisms induce the release of profibrotic mediators like FGF, VEGF, and PDGF, which trigger inflammation and angiogenesis, as well as fibroblast proliferation, migration, transformation to myofibroblasts, and survival. This results in fibrosis of the affected tissue.1,3-7

OFEV Mechanism Of Action IPF

Adapted from Wollin L et al. J Scleroderma Relat Disord. 2019;4(3):212-218.

Cyendiv® mechanism of action1,3-7

Cyendiv® acts on the self-sustaining fibrotic processes that can occur in SSc-ILD, IPF, and other chronic fibrosing ILDs with a progressive phenotype through the inhibition of key kinases such as PDGFR, FGFR, VEGFR, CSF1R, and Lck2.5-7

Mechanism of action of CYENDIV showing it blocking PDGFR, FGFR, VEGFR, CSF1R and Lck and inhibiting fibrosis

Adapted from Wollin L et al. J Scleroderma Relat Disord. 2019;4(3):212-218.

SSc-ILD pathogenesis

Published May 01, 2020 by Boehringer Ingelheim

Understand the mechanism of disease and the pathophysiology of pulmonary fibrosis in patients with SSc-ILD

 

Footnotes

Akt, protein kinase b; CSF1R, colony-stimulating factor 1 receptor; ECM, extracellular matrix; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; Lck, lymphocyte-specific tyrosine-protein kinase; PDGF, platelet-derived growth factor; PDGFR, platelet-derived growth factor receptor; SSc-ILD, systemic sclerosis-associated interstitial lung disease; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

References

  1. Cyendiv® India pack insert version dated
  2. Distler O, et al; the SENSCIS Trial Investigators. Nintedanib for systemic sclerosis-associated lung disease. N Engl J Med. 2019;380(26):2518-2528. doi:10.1056/NEJMoa1903076.
  3. Hilberg F, et al. BIBF 1120: Triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68(12):4774-4782.
  4. Wollin L, et al. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014;349(2):209-220.
  5. Wollin L, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1434-1445.
  6. Wollin L, et al. Rationale for the evaluation of nintedanib as a treatment for systemic sclerosis–associated interstitial lung disease. JSRD. 2019;4(3):212-218.
  7. Wollin L, et al. Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases. Eur Respir J. 2019;54:1900161.
  8. Flaherty KR, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681.