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Updated: Jul 16, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Small molecule antagonists of the TGF-beta1/TGF-beta receptor binding interaction
James K Burmester1, Sherry A Salzman, Kai Qi Zhang
1Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield Clinic, Marshfield, WI 54449, USA. burmester.jim@mcrf.mfldclin.edu
Abstract:
Excessive and inappropriate action of transforming growth factor (TGF)-beta has been implicated in the pathogenesis of several disease processes, especially cancer and fibrosis. To identify antagonists of the TGF- beta ligand-binding domain that may have therapeutic potential, we screened the National Cancer Institute open access chemical repository for molecules that inhibited binding of TGF-beta to the type II receptor (TbetaRII). About 30,000 molecules were screened resulting in the identification of five structurally related molecules that reduced binding of TGF-beta1 to soluble TbetaRII with an ED50 of approx 10 microM. The chemicals blocked inhibition of Mv1Lu cell growth by TGF-beta, TGF-beta - induced expression of luciferase driven by the TGF-beta response element, and induction of plasminogen inhibitor mRNA detected by Northern blot. In contrast, the chemicals did not block activin-induced inhibition of cell growth. Our results identify a novel chemical group that blocks binding of TGF-beta to its receptor and may result in novel treatment for disease.
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