olitigaltin (GB0139) / Damora Therapeutics - LARVOL DELTA

Guanxinshu attenuates atherosclerosis by suppressing Galectin-3-mediated NLRP3 inflammasome activation. (PubMed, J Mol Histol) - "Mice were divided into five groups: control, model, low-dose GXS (12.5 g/kg/day), high-dose GXS (25 g/kg/day), and simvastatin...Human coronary artery endothelial cells (HCAECs) were treated with oxidized LDL (ox-LDL) to establish an injury model, followed by intervention with GXS-containing serum or the Gal-3 inhibitor TD139...Molecular docking predicted potential binding between representative candidate components of GXS and Gal-3, as well as potential binding affinity between Gal-3 and NLRP3 proteins. This study demonstrates for the first time that GXS mitigates vascular inflammation and slows AS progression by modulating Gal-3/NLRP3 inflammasome-associated signaling and reducing NLRP3 inflammasome-associated protein expression."

Journal • Atherosclerosis • Cardiovascular • Inflammation • APOE • IL18 • IL1B • IL6 • LGALS3 • NLRP3 • TNFA

Platelet glycoprotein VI exacerbates folic acid–induced acute kidney injury via interaction with galectin-3 secreted by tubular epithelial cells (ISTH 2026) - "The study utilized GPVI-specific knockout mice and TD139, a small-molecule galectin-3 inhibitor...Targeting the galectin-3-GPVI interaction represents a promising novel therapeutic strategy for AKI. DOI*10.1016/j.rpth.2026.105150"

Acute Kidney Injury • Inflammation • Nephrology • Renal Disease

Effects of Galectin-3 inhibitors paired with direct current stimulation in preclinical models of aggressive meningioma. (PubMed, Mol Biol Rep) - "Methods We evaluated the effects of the Gal-3 inhibitor TD139 combined with either low-intensity direct current electrostimulation (DCES) on meningioma cells in a human co-culture model, or non-invasive transcranial direct current stimulation (tDCS) in an orthotopic preclinical model...This combination treatment was also associated with a significant decrease in the meningioma-associated marker NDRG4 and the proliferation marker Ki-67. Conclusion The results indicate that combining Gal-3 inhibitors with direct current stimulation has potential as an effective treatment modality for aggressive meningiomas."

Journal • Preclinical • Brain Cancer • Meningioma • Oncology • Solid Tumor • CD4 • LGALS3

Microglial galectin-3 disrupts parvalbumin interneurons and hippocampal synchrony, driving cognitive deficits. (PubMed, J Neuroinflammation) - "Supporting this pathogenic cascade, pharmacological inhibition of Gal-3 with TD139 effectively suppresses TLR2/inflammasome activation, attenuates oxidative stress, and prevents memory deficits...Finally, chemogenetic reactivation of hippocampal PV interneurons using DREADDs restores theta/gamma oscillations and ameliorates LPS-induced cognitive deficits. Together, our findings define a coherent pathogenic axis linking microglial Gal-3 upregulation to PV interneuron-dependent network desynchronization and highlight Gal-3 as a promising therapeutic target for inflammation-associated cognitive disorders."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Infectious Disease • Inflammation • Septic Shock • LGALS3 • NLRP3 • TLR2

Galectin-3 in microglia mediates neuroinflammation-induced cognitive dysfunction via selective elimination of excitatory synapses in hippocampal CA1. (PubMed, Brain Res) - "Systemic pharmacologic inhibition with TD139 and microglia-targeted Lgals3 knockdown (AAV-shLgals3 in Cx3cr1-CreERT2 mice) preserved excitatory synapses, restored CA1 gamma power, and improved cognitive performance in the neuroinflammation model. These results identify Gal-3-dependent microglial phagocytosis as a key mechanism linking neuroinflammation to cognitive dysfunction."

Journal • CNS Disorders • Cognitive Disorders • Inflammation • CX3CR1 • LGALS3

Investigating the role of Galectin-3 in a model of lung granuloma formation (IMMUNOLOGY 2026) - "Histiocytes play a critical role in granuloma formation and maintenance. Galectin-3 can serve as a marker for histiocytes and may be a promising target for therapies aimed at treating granulomatous diseases."

Infectious Disease • Inflammation • LGALS3

Galectin-3 mediates lysosome-related inflammation within monocyte-derived macrophages in a mouse model of ischemic brain injury. (PubMed, J Clin Invest) - "Systemic and transient TD139 treatment in the acute injury phase reduced infarcts, tempered neuroinflammation, and improved long-term neurological outcomes. Therefore, MDMø-derived GAL3 represents a drug target that could be accessed in peripheral blood to potentially mitigate post-stroke brain injury."

Journal • Preclinical • Cardiovascular • CNS Disorders • Inflammation • Transplantation • Vascular Neurology • LGALS3

A patent review of galectin-1 and galectin-3 inhibitors and their potential therapeutic applications (2022-present): an update. (PubMed, Expert Opin Ther Pat) - "The patent landscape is dominated by β-D-galactopyranose and thiodigalactoside scaffolds, with limited innovation and unresolved issues in selectivity, drug-likeness, and efficacy, highlighted by GB0139's Phase II failure...Yet, robust biochemical data and structural proof of binding remain scarce. To move the field forward, future patents must diversify chemotypes, substantiate binding modes with crystallography or NMR, and demonstrate translation in relevant disease models."

Journal • Review • Immune Modulation • Immunology • Oncology • LGALS1 • LGALS3

Galectin-3 exacerbates autoimmune diabetes by limiting regulatory T cell differentiation and function. (PubMed, Sci Adv) - "Mechanistically, Galectin-3 bound to and activated lymphocyte activation gene 3 (LAG3), a receptor expressed on activated T cells, subsequently suppressing the MEK/ERK signaling pathway and thereby hindering Treg cell differentiation and function. In summary, our study identifies Galectin-3 as a potential biomarker for T1D and suggests that TD139 holds promise as a therapeutic candidate for patients with T1D and high serum Galectin-3 levels."

Biomarker • IO biomarker • Journal • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • LAG3 • LGALS3

Differential Expression of IFI16, IL-33 and CD55 Link Potential Common Pathogenic Mechanisms for COVID-19 and Ulcerative Colitis. (PubMed, J Multidiscip Healthc) - "Drug repurposing efforts prioritized retinoic acid, cyclosporine, and TD-139, which target these shared mechanisms. This study reveals robust molecular commonalities between COVID-19 and UC, highlighting dysregulated immune pathways and regulatory networks as shared mechanisms. We propose novel drug-repurposing candidates supported by network-based evidence, offering potential therapeutic strategies for patients with comorbid COVID-19 and UC."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Respiratory Diseases • Ulcerative Colitis • CD55 • IFI16 • IL33 • MIR155 • STAT1

Pathways in the brain, heart and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence. (PubMed, Cardiooncology) - "This study highlights probable hub genes, drugs targeting them, and associated pathways perturbed by SARS-CoV-2 NSP6. Galectin3 (LGALS3) upregulated in both heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies for present scenario of long and recurrent COVID-19."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Lung Cancer • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • ATP6AP1 • ATP6V1D • CANX • CCNA1 • CCNB1 • CCND1 • CCNE1 • CDKN1B • EGF • LAMP2 • LGALS3 • TGFB1 • TGFBR2

Integration of single-cell and bulk RNA sequencing data to identify liquid-liquid phase separation-related prognostic biomarkers in hepatocellular carcinoma. (PubMed, Sci Rep) - "Ten LLPSRGs were identified as part of the LLPS-related risk signature, and potential agents were predicted: Olitigaltin and Lactose for LGALS3, and Sitamaquine, Phenazopyridine, Sulfanilamide, Pamaquine, Sodium ascorbate, and Co-trimoxazole for G6PD. Knockdown of LGALS3 inhibited HCC cell migration and invasion. LLPS-related molecular characteristics were identified, and an LLPS-related prognostic model was developed, offering novel insights into HCC research and providing potential therapeutic targets."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CXCR4 • EGFR • LGALS3

Protocol for isolating patient-derived ascites cells and extracellular vesicles from gastric cancer peritoneal metastases. (PubMed, STAR Protoc) - "This protocol also includes TD-139 loading into exosomes for functional assays to evaluate their role in modulating the tumor microenvironment. For complete details on the use and execution of this protocol, please refer to Fan et al.1."

Journal • Gastric Cancer • Oncology • Peritoneal Cancer • Solid Tumor

Pleiotropic regulatory mechanisms and targeted therapeutic prospects of Galectin-3 in aging-related diseases. (PubMed, Neurotherapeutics) - "Preclinical studies demonstrate that Gal-3-targeted interventions-including small-molecule inhibitors (e.g., TD-139), natural compounds (e.g., modified citrus pectin), and other pharmacological agents-exert neuroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects by binding to Gal-3 and modulating its activity in animal models, offering promising avenues for multi-disease treatment. However, the dual roles and complex regulatory networks of Gal-3 present challenges for clinical translation, requiring context-specific therapeutic approaches tailored to distinct disease mechanisms. Future research should focus on elucidating tissue-specific mechanisms and optimizing combination therapies to enable precise targeting of aging-related pathologies."

Journal • Review • Age-related Macular Degeneration • Alzheimer's Disease • Atherosclerosis • Cardiovascular • CNS Disorders • Diabetes • Immunology • Inflammation • Macular Degeneration • Metabolic Disorders • Movement Disorders • Ophthalmology • Osteoarthritis • Pain • Parkinson's Disease • Retinal Disorders • Rheumatology • Type 2 Diabetes Mellitus • LGALS3

Intracellular Galectin-3 as a Crucial Regulator of Foam Cell Formation and Apoptosis Progression through the Modulation of Membrane Lipid Rafts. (PubMed, Arch Med Res) - "Gal-3 modulates lipid raft organization and oxLDL internalization, acting as a pro-inflammatory mediator in foam cell biology. These findings highlight Gal-3 as a potential therapeutic target for early atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • Cholera • Inflammation • Metabolic Disorders • CD14 • CD36 • LGALS3 • SCARB1

DEFINE - Evaluating Therapies for COVID-19 (clinicaltrials.gov) - P1/2 | N=71 | Completed | Sponsor: University of Edinburgh | Recruiting ➔ Completed | N=200 ➔ 71

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease

Inhibition of Galectin-3 Expression Could Preserve the Immunoregulatory Function of Mesenchymal Stem Cells During Cell Passaging. (PubMed, Front Biosci (Landmark Ed)) - "Gal-3 contributes to the decline in the immunomodulatory capabilities of MSCs. TD139, a Gal-3 inhibitor, has a potentially positive effect on rescuing the immunoregulation dysfunction of MSCs in late-passage and may represent a novel strategy to enhance the therapeutic potential of late-passage MSCs for GVHD treatment."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation • LGALS3

Lectins and neurodegeneration: A glycobiologist's perspective. (PubMed, Adv Clin Exp Med) - "Overexpression of this lectin under inflammatory conditions activates TREM2 and TLR4 signaling pathways, enhances the phagocytic activity of microglia and leads to tissue damage. Blocking Gal-3 interactions with the thiodigalactoside inhibitor (TD-139) appears to be a promising novel approach to pharmacologically alleviating neuroinflammation."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • LGALS3

Binding free energy analysis of galectin-3 natural ligands and synthetic inhibitors. (PubMed, Protein Sci) - "Synthetic drug molecules GB0139, GB1107, and GB1211 were estimated to have binding free energies of -4.3, -6.7, and -9.5 kcal/mol respectively. We find that while the hydroxyl groups of the natural ligands interact reasonably well with residues in galectin-3's binding pocket, structural dynamics weaken the binding pose and favor interactions with water, sometimes yielding to dissociation. In contrast, the more favorable binding energy of GB1211, leading inhibitor in clinical studies, is associated with strong and constant electric fields across the bonds investigated, suggesting a stiffer binding pose with a stabilizing σ-hole interaction."

Journal

Targeting Galectin-3 to modulate inflammation in LAMA2-deficient congenital muscular dystrophy. (PubMed, bioRxiv) - "RNA sequencing of TD-139-treated dyW muscles showed upregulation of muscle contraction pathways and downregulation of fibrosis-related genes. These findings highlight Galectin-3 + macrophages as key contributors to LAMA2-CMD pathophysiology and support further exploration of TD-139 as a potential therapeutic strategy for LAMA2-CMD and other dystrophic conditions driven by chronic inflammation."

Journal • CNS Disorders • Fibrosis • Immunology • Inflammation • Muscular Dystrophy • LAMA2 • LGALS3 • PTPRC

Platelet glycoprotein VI promotes folic acid-induced acute kidney injury through interaction with tubular epithelial cell-derived galectin-3. (PubMed, Cell Commun Signal) - "These findings suggest that galectin-3, which is released from damaged cells during acute kidney injury (AKI), exacerbates renal inflammation and tissue damage by activating platelets through glycoprotein VI (GPVI). This activation enhances interactions between monocytes and platelets, ultimately leading to the formation of monocyte-platelet aggregates (MPA) and the polarization of M1 macrophages."

Journal • Acute Kidney Injury • Inflammation • Nephrology • Renal Disease • CD68 • ITGA2B

DEFINE - Evaluating Therapies for COVID-19 (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: University of Edinburgh | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Intravitreal injection of the Galectin-3 inhibitor TD139 provides neuroprotection in a rat model of ocular hypertensive glaucoma. (PubMed, Mol Brain) - "The degeneration of retinal ganglion cells was prevented by TD139 injection, but gross glial markers remained unaffected. These data confirm that the intravitreal injection of TD139 is neuroprotective in a rat ocular hypertensive model of glaucoma, while suggesting that the inhibition of Galectin-3 is not sufficient to alter the gross inflammatory outcome."

Journal • Preclinical • Cardiovascular • CNS Disorders • Glaucoma • Inflammation • Ocular Inflammation • Ophthalmology

Galectin-3 inhibition reduces fibrotic scarring and promotes functional recovery after spinal cord injury in mice. (PubMed, Cell Biosci) - "Our finding underscores the pivotal role of macrophage-derived Galectin-3 in modulating the sustained internalized activation of PDGFRβ within fibroblasts, providing a novel mechanistic insight into fibrotic scarring post-SCI."

Journal • Preclinical • CNS Disorders • Fibrosis • Immunology • Orthopedics • LGALS3 • PDGFRB

In vitro and in vivo effects of Galectin-3 inhibitor TD139 on inflammation and ERK/JNK/p38 pathway in gestational diabetes mellitus. (PubMed, Kaohsiung J Med Sci) - "The study used TNF-α to mimic GDM in placental tissues and an STZ-induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy."

Journal • Preclinical • Diabetes • Gestational Diabetes • Inflammation • Metabolic Disorders • Oncology • IL1B • IL6 • LGALS3 • MAPK8 • TNFA