SIS3

SIS3 (SMAD3 Inhibitor Selective 3) is a cell-permeable, selective small-molecule inhibitor of Smad3 phosphorylation. It specifically blocks the TGF-β1-induced phosphorylation of Smad3 and its subsequent nuclear translocation and transcriptional activity, without affecting the phosphorylation of Smad2 or other signaling pathways such as p38 MAPK, ERK, or JNK. By inhibiting the TGF-β/Smad3 signaling axis, SIS3 effectively suppresses pro-fibrotic responses, epithelial-mesenchymal transition (EMT), and immunosuppressive tumor microenvironments. It is widely utilized as a pharmacological research tool to investigate the role of Smad3 in various pathologies, including pulmonary and renal fibrosis, cardiac aging, and several cancers such as osteosarcoma and lung cancer. Recent research has also explored its delivery via novel platforms like nanoemulsions and hydrogels to enhance therapeutic efficacy in preclinical models.

Other names

SMAD3 Inhibitor Selective 3SMAD-3 Inhibitor Selective 3SMAD 3 Inhibitor Selective 36,7-Dimethoxy-2-((2E)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-propenoyl)-1,2,3,4-tetrahydroisoquinoline