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Updated: Jan 4, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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A new FGFR inhibitor disrupts the TGF-β1-induced fibrotic process

Mi-Hyoung Kim1,2, Seung-Youn Jung1, Kyung-Hee Song1

  • 1Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.

Journal of Cellular and Molecular Medicine
|November 7, 2019
PubMed

Insights

A new compound, IM-1918, shows promise in treating pulmonary fibrosis (PF). It effectively reduced fibrotic markers in human lung cells and a mouse model, suggesting potential therapeutic benefits for this irreversible lung disease.

Area of Science:

  • Pharmacology
  • Pulmonary Medicine
  • Fibrosis Research

Background:

  • Pulmonary fibrosis (PF) is a chronic, irreversible lung disease marked by fibroblast activation and matrix deposition.
  • Current anti-fibrotic therapies offer limited improvement, highlighting the need for novel treatments.

Purpose of the Study:

  • To investigate the anti-fibrotic potential of a novel imidazopurine compound, IM-1918.
  • To elucidate the molecular mechanisms underlying IM-1918's effects on lung fibroblasts and a fibrosis model.

Main Methods:

  • In vitro: Assessed IM-1918's effect on TGF-β-stimulated reporter activity and fibrotic marker expression in human lung fibroblasts.
  • Investigated IM-1918's impact on key signaling pathways including Smad, MAPK, Akt, ERK, and FGFR phosphorylation.
  • In vivo: Evaluated IM-1918's efficacy in a bleomycin-induced murine lung fibrosis model.

Main Results:

  • IM-1918 significantly inhibited TGF-β-stimulated reporter activity and reduced fibrotic markers (CTGF, fibronectin, collagen, α-SMA) in lung fibroblasts.
  • IM-1918 modulated Akt, ERK1/2, and FGFR1/3 phosphorylation, distinct from Smad and p38/JNK pathways.
  • In vivo, IM-1918 markedly reduced lung fibrotic areas, collagen, and α-SMA accumulation in a bleomycin-induced fibrosis model.

Conclusions:

  • IM-1918 demonstrates significant anti-fibrotic activity in both in vitro and in vivo models.
  • The compound's mechanism involves modulation of Akt, ERK, and FGFR signaling pathways.
  • IM-1918 represents a promising therapeutic candidate for treating pulmonary fibrosis.
Keywords:
Aktextracellular signal-regulated kinase 1/2fibroblast growth factor receptorimidazopurinelung fibrosistransforming growth factor-β

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