galectin 3 inhibitor belapectin  (Galectin Therapeutics)

Journal: Advanced Science

Article Title: A Dynamic DNA Nano‐Antioxidant Targeting Galectin‐3 Attenuates Liver Fibrosis via Reducing Macrophage Oxidative Stress

doi: 10.1002/advs.202509977

Figure Lengend Snippet: Galectin‐3 in macrophages promoted liver fibrosis. A) 12 clusters of 66135 cells from healthy (n = 5) and fibrotic (n = 5) livers; B) Clustering 66135 cells from healthy (n = 5) and fibrotic (n = 5) human livers, annotating injury condition; C) The expression of LGALS3 in the 66135 cells; D) The expression of LGALS3 in different clusters of cells; E) Representative immunofluorescence images of Galectin‐3, collagen‐1, and DAPI in both healthy and fibrotic livers. Representative Sirius red images in both healthy and fibrotic livers (right). Scale bar = 50 µm; F) Graphs showed the correlation between the Galectin‐3 positive staining and collagen‐1 positive staining in healthy (n = 11) and fibrotic (n = 16) human livers; G) Graphs showed the correlation between the Galectin‐3 positive staining and Ishak scores in healthy (n = 7) and fibrotic (n = 10) human livers; H) Representative western blotting images of Galectin‐3 expression in healthy (n = 3) and fibrotic (n = 3) human livers; I) Statistic analysis of (H). Data are presented as the mean ± SD (n = 12). *** P < 0.001; J) Representative western blotting images and statistical analysis of Galectin‐3 expression in olive oil (n = 3) and CCl 4 (n = 3) treated mouse livers; K) Statistical analysis of (J). Data are presented as the mean ± SD (n = 3). **** P < 0.0001; L) Representative immunofluorescence images of Galectin‐3, collagen‐1, F4/80 and DAPI in both olive oil and CCl 4 treated mouse livers. Scale bar = 50 µm; M) Graphs showed the correlation between the Galectin‐3 positive staining and collagen‐1 positive staining in olive oil (n = 7) and CCl 4 (n = 8) treated mouse livers; N) Graphs showed the correlation between the Galectin‐3 positive staining and F4/80 positive staining in olive oil (n = 7) and CCl 4 (n = 8) treated mouse livers.

Article Snippet: [ , , ] Early‐phase clinical evaluation of the small‐molecule Galectin‐3 inhibitor Belapectin (GR‐MD‐02) yielded promising results, with significant improvements in FibroTest scores.

Techniques: Expressing, Immunofluorescence, Staining, Western Blot

Journal: Advanced Science

Article Title: A Dynamic DNA Nano‐Antioxidant Targeting Galectin‐3 Attenuates Liver Fibrosis via Reducing Macrophage Oxidative Stress

doi: 10.1002/advs.202509977

Figure Lengend Snippet: Preparation and characterization of DDN.A) RAW264.7 cells were transfected with PBS, siRNA1, siRNA2, or siRNA3, then treated with PBS or LPS + IFN‐γ. Representative western blotting images of Galectin‐3 expression in each group; B) Statistical analysis of (A). Data are presented as the mean ± SD (n = 3). *** P < 0.001, **** P < 0.0001; C) The expression of Lgals3 in each group. Data are presented as the mean ± SD (n = 3). **** P < 0.0001; D) Schematic illustration of the self‐assembly synthesis process of DDN; E) AGE showed the stepwise construction of the DDN. Lane 1: SH1; lane 2: SH2; lane 3: SH3; lane 4: SH1+ SH2; lane 5: SH1+ SH2+SH3; lane 6: SH1+ SH2+SH3+ siRNA; lane 7: SH1+ SH2+SH3+ 2 siRNA; lane 8: SH1+ SH2+SH3+ 3 siRNA (DDN); lane 9: tFNA. Red: Cy5 channel; blue: Gel Red channel; F) High‐performance capillary electrophoresis (HPCE) showed the stepwise construction of the DDN. The order of lanes 1–9 is the same as (E); G) The size of DDN; H) The ζ potential of DDN; I) The TEM images of DDN. Scale bar = 20 nm; J) The AFM images of DDN. Scale bar = 20 nm; K) The fluorescence images of RAW264.7 cells that were treated with PBS, Cy5‐siRNA, Cy5‐tFNA, Cy5‐DDN, or Cy5‐siRNA‐lip at 6 h. Scale bar = 25 µm; L) Statistic analysis of (K). Data are presented as the mean ± SD (n = 3). **** P < 0.0001; M) RAW264.7 cells were transfected with PBS, DDN, or siRNA‐lip, then treated with PBS or LPS + IFN‐γ. Representative western blotting images of Galectin‐3 expression in each group; N) Statistic analysis of (M). Data are presented as the mean ± SD (n = 3). **** P < 0.0001; O) The expression of Lgals3 of in each group. Data are presented as the mean ± SD (n = 3). **** P < 0.0001.

Article Snippet: [ , , ] Early‐phase clinical evaluation of the small‐molecule Galectin‐3 inhibitor Belapectin (GR‐MD‐02) yielded promising results, with significant improvements in FibroTest scores.

Techniques: Transfection, Western Blot, Expressing, Electrophoresis, Fluorescence

Journal: Advanced Science

Article Title: A Dynamic DNA Nano‐Antioxidant Targeting Galectin‐3 Attenuates Liver Fibrosis via Reducing Macrophage Oxidative Stress

doi: 10.1002/advs.202509977

Figure Lengend Snippet: DDN restrained the exhaustion of NRF2 via silencing Galectin‐3 expression. A) RAW264.7 cells were treated with PBS or DDN, then stimulated with LPS + IFN‐γ. The RAW264.7 cells were collected and performed to RNA‐seq. Heatmaps of differentially expressed genes among the groups; B) Bubble diagram showed the top 20 significantly enriched GO terms; C) Petal diagram showed the top 20 significantly enriched GO terms; D) Schematic illustration of DDN‐mediated reduction in LPS and IFN‐γ induced macrophage oxidative stress and ROS release through Galectin‐3 suppression and subsequent prevention of NRF2 depletion; E) RAW264.7 cells were treated with PBS or DDN, then stimulated with LPS + IFN‐γ by different time points. Representative western blotting images of Galectin‐3 and NRF2 expression in each group; F,G) Statistic analysis of (K). Data are presented as the mean ± SD (n = 6). * P < 0.05, ** P < 0.01, **** P < 0.0001; H,I) The expression of Lgals3 and Nrf2 in each group. Data are presented as the mean ± SD (n = 6). ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: [ , , ] Early‐phase clinical evaluation of the small‐molecule Galectin‐3 inhibitor Belapectin (GR‐MD‐02) yielded promising results, with significant improvements in FibroTest scores.

Techniques: Expressing, RNA Sequencing, Western Blot

Journal: Advanced Science

Article Title: A Dynamic DNA Nano‐Antioxidant Targeting Galectin‐3 Attenuates Liver Fibrosis via Reducing Macrophage Oxidative Stress

doi: 10.1002/advs.202509977

Figure Lengend Snippet: Reduction of liver fibrosis by DDN.A) Schematic illustration of the treatment protocol in the chronic liver fibrosis mouse model; B) Effects of different treatments (Olive oil, CCl 4 + PBS, CCl 4 + siRNA, CCl 4 + tFNA, CCl 4 + DDN) on liver function indicators, including ALB, ALT, AST, and UREA levels; C) Representative H&E staining image, Sirius red staining images and immunofluorescence images of αSMA, collagen‐1 and DAPI of liver in each group; black scale bar = 100 µm, white scale bar = 50 µm; D) Representative western blotting images of NRF2, Galectin‐3, collagen‐1, and αSMA expression in each group; E) Statistic analysis of (D), Data are presented as the mean ± SD (n = 6). ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: [ , , ] Early‐phase clinical evaluation of the small‐molecule Galectin‐3 inhibitor Belapectin (GR‐MD‐02) yielded promising results, with significant improvements in FibroTest scores.

Techniques: Staining, Immunofluorescence, Western Blot, Expressing

Journal: Advanced Science

Article Title: A Dynamic DNA Nano‐Antioxidant Targeting Galectin‐3 Attenuates Liver Fibrosis via Reducing Macrophage Oxidative Stress

doi: 10.1002/advs.202509977

Figure Lengend Snippet: Proposed mechanisms of DDN. SH1, SH2, SH3, and siRNA undergo self‐assembly to form DDN, which are delivered via i.p. injection into the mesenteric venous system. Following entry into systemic circulation, DDN are preferentially transported via the portal venous system to the liver, where they are efficiently internalized by hepatic macrophages. Intracellular release of siRNA payload from DDN effectively downregulates expression of Galectin‐3, thereby preventing NRF2 depletion and restoring cellular antioxidant defense mechanisms. This process significantly reduces ROS generation and release. The consequent polarization of macrophages toward an anti‐inflammatory phenotype contributes to the amelioration of liver fibrosis.

Article Snippet: [ , , ] Early‐phase clinical evaluation of the small‐molecule Galectin‐3 inhibitor Belapectin (GR‐MD‐02) yielded promising results, with significant improvements in FibroTest scores.

Techniques: Injection, Expressing

Journal: International Journal of Molecular Sciences

Article Title: Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis

doi: 10.3390/ijms26041778

Figure Lengend Snippet: Class of considered drugs for treating MASH/MASLD.

Article Snippet: , Galectin-3 inhibitor , Belapectin [ , ] , Inhibits galectin-3, targeting fibrosis and inflammation pathways , Large molecule galactoarabino-rhamnogalacturonan polysaccharide inhibitor derived from natural sources; prevents formation of oligomeric structures and lattice-like assemblies that are essential for activating pro-fibrotic signaling pathways, thereby halting fibrosis and reducing liver inflammation.

Techniques: Drug discovery, Control, Clinical Proteomics, Variant Assay, Expressing, Allele-specific Oligonucleotide, Activity Assay, Activation Assay, Derivative Assay, Protein-Protein interactions, Probiotics, Produced, Bacteria, Transplantation Assay