A novel small compound that antagonizes TGF-β/Smad signaling ameliorates bleomycin-induced skin fibrosis

Objective: Systemic sclerosis is a connective tissue disease characterized by tissue fibrosis in the skin and internal organs. Transforming growth factor beta (TGF-β) is well known to play a crucial role in the pathogenesis of systemic sclerosis. The compound named Histidine-Pyridine-Histidine (HPH) is an oxygen-activating ligand derived from the structure of bleomycin. We synthesized HPH derivatives and discovered HPH-15 that antagonizes TGF-β/Smad signaling. In this study, we assessed the utility of HPH-15 in a mouse model of systemic sclerosis.