Small molecule drugs with TGFbeta signaling activity

The TGF-beta signaling pathway is a key regulator of many biological processes and is involved in the pathogenesis of major diseases. Regulating this pathway could have broad application to treating neurodegenerative diseases, stroke, tumors, wound healing etc. Stanford researchers used a Smad based reporter cell line from a TGF-b1 knockout mouse to search for small chemical molecules that activate Smad signaling. Three lead structures that show signaling activity in cell culture and in a Smad reporter mouse in vivo were identified. The small chemical compounds discovered here have TGF-beta agonist activity and involve novel chemical structures. The compounds are active in vivo in the CNS and activate Smad-dependent genes, independent of the TGF-beta receptor. These compounds could therefore potentially be used to treat tumors that downmodulated TGF receptors, and they could activate TGF signaling in wound healing, stroke, or neurodegeneration.