| abstract |
The present disclosure relates to compounds, compositions and methods for the treatment of diseases through inhibiting the activity of the transforming growth factor beta (TGF-β). More specifically, the disclosed compounds, compositions and methods are useful in the treatment of certain cancers (e.g. multiple myeloma, hematologic malignancies), diseases associated with excessive TGF-β activity including fibrosis, dermal scarring, immune dysfunction, and bone loss by inhibiting the conversion of latent TGF-β to active TGF-β. A method of preventing the activation of TGF-β in pathology is also provided, comprising administering an amount of the compounds sufficient to inhibit conversion of latent TGF-β to active TGF-β by thrombospondin 1 (TSP1), resulting in reduced TGF-β activity and reduced adverse effects such as fibrosis, bone loss, and immune dysfunction. |