A5043003994- Galectins and Cancer Biology
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Helicobacter pylori-related gastroenterology studies
- Toxin Mechanisms and Immunotoxins
- RNA modifications and cancer
- Pancreatitis Pathology and Treatment
- Signaling Pathways in Disease
- Immune Cell Function and Interaction
- Inflammation biomarkers and pathways
- Photochemistry and Electron Transfer Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Macrophage Migration Inhibitory Factor
- Electrochemical Analysis and Applications
- Amoebic Infections and Treatments
- Radical Photochemical Reactions
- Protein Tyrosine Phosphatases
Galecto (Denmark)
2019-2024
National Research Council Canada
1988
Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 novel potent small-molecule inhibitor Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess safety, tolerability, pharmacokinetics pharmacodynamics inhaled 36 healthy subjects 24 patients with IPF. Six dose cohorts six were evaluated (4:2 TD139:placebo ratio) single...
Abstract A combination therapy approach is required to improve tumor immune infiltration and patient response checkpoint inhibitors that target negative regulatory receptors. Galectin-3 a β-galactoside-binding lectin highly expressed within the microenvironment of aggressive cancers whose expression correlates with poor survival particularly in patients non–small cell lung cancer (NSCLC). To examine role galectin-3 inhibition NSCLC, we tested effects depletion using genetic pharmacologic...
Galectin-3 is a carbohydrate-binding protein central to regulating mechanisms of diseases such as fibrosis, cancer, metabolic, inflammatory, and heart disease. We recently found high affinity (nM) thiodigalactoside GB0139 which currently in clinical development (PhIIb) an inhaled treatment idiopathic pulmonary fibrosis. To enable systemically galectin-3 driven disease, we here present the first series selective inhibitors combining with oral bioavailability. This was achieved by optimizing...
High circulating galectin-3 is associated with poor outcomes in patients coronavirus disease (COVID-19). We hypothesized that GB0139, a potent inhaled thiodigalactoside inhibitor antiinflammatory and antifibrotic actions, would be safely effectively delivered COVID-19 pneumonitis.
Abstract Purpose Galectin-3, a β-galactoside-binding lectin, plays key role in several cellular pathways involved chronic inflammation, heart disease and cancer. GB1211 is an orally bioavailable galectin-3 inhibitor, developed to be systemically active. We report safety pharmacokinetics (PK) of healthy participants. Methods This phase 1, double-blind, placebo-controlled, first-in-human study (NCT03809052) included single ascending-dose (with food-effect cohort) where participants across...
Abstract Rationale High galectin-3 levels predict poor outcomes in patients with COVID-19. Galectin-3 activates monocytes and macrophages which are directly implicated COVID-19 immunopathology the cytokine storm. GB0139 is a potent thiodigalactoside inhibitor may reduce severe effects of disease. We report safety pharmacokinetics pharmacodynamics inhaled inhibitor, GB0139, assess clinical key systemic inflammatory biomarkers hospitalised (ClinicalTrials.gov/EudraCT identifier: NCT04473053...
The interest in galectin-3 as a drug target the cancer and fibrosis space has grown during past few years with several new classes of compounds being developed. first orally available inhibitor,
<div>Abstract<p>A combination therapy approach is required to improve tumor immune infiltration and patient response checkpoint inhibitors that target negative regulatory receptors. Galectin-3 a β-galactoside-binding lectin highly expressed within the microenvironment of aggressive cancers whose expression correlates with poor survival particularly in patients non–small cell lung cancer (NSCLC). To examine role galectin-3 inhibition NSCLC, we tested effects depletion using...
<p>Supplementary methods and figure legends</p>
<p>Figure S1 Anti-galectin-3 antibodies do not correlate with decreased tumor volume in galectin-3-/- mice. Figure S2 Effect of DT administration CD11b-DTR mice on TAMs.</p>
<p>Figure S3 Galectin-3 knockdown impairs LLC1 cell proliferation in vitro but not vivo. Figure S4 GB1107 has good oral bioavailability mice.</p>
<p>Figure S7 Flow cytometric analysis of bone marrow from WT or galectin-3-/- mice. Figure S8 GB1107 and anti-PD-L1 therapy is associated with reduced intra-tumor galectin-3 increased CD8+ T cell infiltration.</p>
<p>Figure S5 GB1107 impairs M2 macrophage differentiation and LLC1 cell migration proliferation in vitro. Figure S6 Flow cytometric analysis of LLC tumors from WT or galectin-3-/- mice.</p>
<p>Figure S3 Galectin-3 knockdown impairs LLC1 cell proliferation in vitro but not vivo. Figure S4 GB1107 has good oral bioavailability mice.</p>
<p>Supplementary methods and figure legends</p>
<p>Figure S5 GB1107 impairs M2 macrophage differentiation and LLC1 cell migration proliferation in vitro. Figure S6 Flow cytometric analysis of LLC tumors from WT or galectin-3-/- mice.</p>
<p>Figure S1 Anti-galectin-3 antibodies do not correlate with decreased tumor volume in galectin-3-/- mice. Figure S2 Effect of DT administration CD11b-DTR mice on TAMs.</p>
<p>Figure S7 Flow cytometric analysis of bone marrow from WT or galectin-3-/- mice. Figure S8 GB1107 and anti-PD-L1 therapy is associated with reduced intra-tumor galectin-3 increased CD8+ T cell infiltration.</p>
<div>Abstract<p>A combination therapy approach is required to improve tumor immune infiltration and patient response checkpoint inhibitors that target negative regulatory receptors. Galectin-3 a β-galactoside-binding lectin highly expressed within the microenvironment of aggressive cancers whose expression correlates with poor survival particularly in patients non–small cell lung cancer (NSCLC). To examine role galectin-3 inhibition NSCLC, we tested effects depletion using...