TD139 is a small molecule inhibitor of inhaled galectin-3 (Gal-3) with potential anti-fibrotic activity, commonly used in the study of idiopathic pulmonary fibrosis.

Galectin-3:7.9 μg/mL, GAL3:0.036 µM (Kd), GAL3:14 nM (Kd)

TD139 has a high affinity for galectin-3 with a Kd of 14 nM and 10 nM for galectin-1, but low affinity for galectins 2, 4N, 4C, 7, 8N, or 9N [1].

In primary lung AECs, TD139 reduces TGF-β1–induced β-catenin translocation to the nucleus, keeping most β-catenin at the cell surface, and blocks TGF-β1–induced β-catenin phosphorylation. TD139 treatment in WT mice results in a marked reduction in lung fibrosis and β-catenin activation, along with decreased galectin-3 expression [1]. Pretreatment of WT C57BL/6 mice with TD139 attenuates liver injury, reduces infiltration of IFNγ-, IL-17-, and IL-4-producing CD4(+) T cells, increases IL-10-producing CD4(+) T cells and F4/80(+) CD206(+) alternatively activated macrophages, and prevents apoptosis of liver-infiltrating MNCs [2].