Galectins form a family of soluble lectins that take part in a wide range of biological processes, such as cell adhesion, cell migration, signaling, intracellular trafficking, cell proliferation, apoptosis, gene expression regulation, inflammation, and immune response. TD 139 is an effective and selective galectin-3 inhibitor with a Kd value of 0.036 µM and Kd values of 2.2 µM and 32 µM for galectin-1 and galectin-7, respectively. TD 139 can be used for the treatment of idiopathic pulmonary fibrosis (IPF)[1]. In primary lung alveolar epithelial cells (AECs), TD 139 (10 µM) reduced TGF-β1–induced β-catenin translocation to the nucleus, with most of the β-catenin remaining at the cell surface. In the lungs of wild-type mice treated with 10 µg TD 139, there was marked reduction in fibrosis and β-catenin activation accompanied by decreased galectin-3 expression. TD 139 produced a significant decrease in total lung collagen[2].
作用机制
TD 139 interacts with the five binding subsites (A–E) that comprise the CRD (carbohydrate recognition domain) of galectin-3[1].
TD139 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Platelet-rich plasma from healthy subjects
1–10 μM
To evaluate the effects of rGalectin-3 on platelet aggregation and ATP release in platelet-rich plasma. Results showed that rGalectin-3 potentiated platelet aggregation and ATP release induced by different agonists.
Am J Respir Crit Care Med. 2012 Mar 1;185(5):537-46.
Hippocampal slices of WT mice
10 µM
15 min
To evaluate the preventive effect of TD139 on gal3-induced degradation of gamma oscillations, results showed that 10 µM TD139 effectively prevented the gal3-induced decrease of gamma oscillation power and rhythmicity
Transl Neurodegener. 2023 Feb 6;12(1):6.
Human neutrophils
250 μM
4 hours
TD139 enhances ROS production in human neutrophils in response to opsonized Candida
Front Immunol. 2017 Feb 3;8:48.
TD139 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Bleomycin-induced lung fibrosis model
Intratracheal administration
10 mg
Administered on Days 18, 20, 22, and 24, continued until Day 26
TD139 significantly reduced lung fibrosis and β-catenin activation.
Am J Respir Crit Care Med. 2012 Mar 1;185(5):537-46.
ApoE−/− mice
Atherosclerosis model
Intraperitoneal injection
15 mg/kg
Twice, 12 hours apart
To evaluate the effects of TD139 on in vivo thrombosis in atherosclerotic ApoE?/? mice. Results showed that TD139 significantly suppressed FeCl3-induced thrombus formation without increasing bleeding risk.
Eur Heart J. 2022 Oct 7;43(37):3556-3574.
Mice
Folic acid-induced acute kidney injury model
Intraperitoneal injection
15 mg/kg
Single injection, observed for 8 days
TD139 significantly improved renal function in AKI mice, reduced platelet and macrophage infiltration, and decreased the expression of inflammatory factors.
Cell Commun Signal. 2025 Mar 21;23(1):148
C57BL/6J mice
Spinal cord injury model (T10 crush injury)
Intrathecal injection
3 µg/µl
Once daily for 14 days
To investigate the effect of TD139 on fibrotic scar formation and functional recovery after spinal cord injury. Results showed that TD139 significantly reduced fibrotic scar formation and promoted neuroprotection and motor function recovery.
Cell Biosci. 2024 Oct 15;14(1):128.
Mice
Light-induced retinal degeneration model
Intraperitoneal injections
15 mg/kg
For five consecutive days, starting one day prior to light exposure
TD139 reduced microglia reactivity and delayed retinal damage
J Neuroinflammation. 2022 Sep 17;19(1):229
Mice
Systemic Candida infection model
Intraperitoneal injection
300 μg
Single dose
TD139-treated mice have enhanced ability to clear the fungus
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