Related Experiment Video

Updated: May 21, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Structural insights and clinical advances in small-molecule inhibitors targeting TGF-β receptor I

Carlota Leonardo-Sousa1, Rodrigo Barriga1, Helena F Florindo1

  • 1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.

Molecular Therapy. Oncology
|March 21, 2025
PubMed

Insights

Small-molecule inhibitors targeting transforming growth factor β receptor I (TGF-βRI) show promise for treating cancer and fibrosis. These TGF-βRI inhibitors may enhance cancer immunotherapy by overcoming treatment resistance.

Area of Science:

  • Molecular Biology
  • Pharmacology
  • Oncology

Background:

  • Dysregulated transforming growth factor β (TGF-β) signaling drives diseases like cancer.
  • TGF-β impedes cancer immunotherapy efficacy, particularly with immune checkpoint inhibitors.
  • Targeting TGF-β receptor I (TGF-βRI) with small molecules offers a therapeutic strategy.

Purpose of the Study:

  • To review the development of small-molecule TGF-βRI inhibitors.
  • To analyze TGF-βRI structural biology and binding interactions.
  • To explore clinical trial data and patent literature for TGF-βRI inhibitors.

Main Methods:

  • Analysis of high-resolution X-ray crystal structures of TGF-βRI.
  • Review of clinical trial data for eight TGF-βRI inhibitors.
  • Survey of patent literature from January 2000 to May 2024.

Main Results:

  • Detailed structural insights into TGF-βRI binding interactions are presented.
  • Eight TGF-βRI inhibitors in clinical trials are discussed regarding mechanism, selectivity, and potential.
  • Over two decades of pharmaceutical innovation in TGF-βRI inhibitor development are summarized.

Conclusions:

  • Consolidated knowledge facilitates the design of next-generation TGF-βRI inhibitors.
  • TGF-βRI inhibitors address unmet needs in oncology and fibrosis.
  • Combining TGF-βRI inhibitors with immune checkpoint inhibitors may enhance cancer immunotherapy.
Keywords:
MT: Regular IssueTGF-βTGF-β receptor ITGF-βRITGF-βRI inhibitorsimmunosuppressiontransforming growth factor β

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