Pulmonary fibrosis, including IPF, is a deadly lung disease that causes respiratory failure and has a median survival rate of 2-3 years.

The disease is primarily driven by the epithelial-mesenchymal transition (EMT) process regulated by transforming growth factor-β1 (TGF-β1), which binds to TGF-β receptor type-I (TGF-β RI) on cell membranes, leading to disease progression.

Small-molecule TGF-β RI inhibitors, such as Vactosertib, offer promising prospects for PF treatment by modulating the TGF-β signaling pathway.

Vactosertib, a small-molecule ALK5 inhibitor, has demonstrated an anti-fibrotic effect by inhibiting both canonical Smad and non-canonical ROS signaling pathways in various fibrotic organs.

It has shown relatively higher potency and low toxicity in animal fibrosis models at low doses. Vactosertib is currently undergoing a phase II clinical trial for various cancers in the USA.

With the potential highlighted by these studies, further clinical research could establish Vactosertib as a highly effective anti-fibrosis drug.