Target Information
| Target General Information | Top | |||||
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| Target ID |
T72038
(Former ID: TTDR00804)
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| Target Name |
Galectin-3 (LGALS3)
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| Synonyms |
Mac-2 antigen; MAC2; Lectin L-29; Laminin-binding protein; L-31; IgE-binding protein; Galactoside-binding protein; Galactose-specific lectin 3; Gal-3; GALBP; Carbohydrate-binding protein 35; Carbohydrate binding protein 35; CBP 35; Beta-galactoside-binding protein LGALS3; 35 kDa lectin
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| Gene Name |
LGALS3
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Hypertension [ICD-11: BA00-BA04] | |||||
| 2 | Idiopathic interstitial pneumonitis [ICD-11: CB03] | |||||
| 3 | Melanoma [ICD-11: 2C30] | |||||
| 4 | Psoriasis [ICD-11: EA90] | |||||
| 5 | Non-alcoholic fatty liver disease [ICD-11: DB92] | |||||
| Function |
May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis. In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells. Together with TRIM16, coordinates the recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1 and BECN1 in response to damaged endomembranes. Galactose-specific lectin which binds IgE.
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| UniProt ID | ||||||
| Sequence |
MADNFSLHDALSGSGNPNPQGWPGAWGNQPAGAGGYPGASYPGAYPGQAPPGAYPGQAPP
GAYPGAPGAYPGAPAPGVYPGPPSGPGAYPSSGQPSATGAYPATGPYGAPAGPLIVPYNL PLPGGVVPRMLITILGTVKPNANRIALDFQRGNDVAFHFNPRFNENNRRVIVCNTKLDNN WGREERQSVFPFESGKPFKIQVLVEPDHFKVAVNDAHLLQYNHRVKKLNEISKLGISGDI DLTSASYTMI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T47F9W | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | GB0139 | Drug Info | Phase 2 | Idiopathic pulmonary fibrosis | [2] | |
| 2 | GR-MD-02 | Drug Info | Phase 2 | Melanoma | [3], [4], [5] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 5 Inhibitor drugs | + | ||||
| 1 | GB0139 | Drug Info | [6] | |||
| 2 | GB0139 | Drug Info | [7] | |||
| 3 | GR-MD-02 | Drug Info | [1] | |||
| 4 | 2,3,5,6-Tetrafluoro-4-Methoxy-Benzamide | Drug Info | [8] | |||
| 5 | PFFFFF | Drug Info | [9] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: GMK | Ligand Info | |||||
| Structure Description | Galectin-3c in complex with Bisamido-thiogalactoside derivate 1 | PDB:4BLI | ||||
| Method | X-ray diffraction | Resolution | 1.08 Å | Mutation | No | [10] |
| PDB Sequence |
MLIVPYNLPL
1122 PGGVVPRMLI1132 TILGTVKPNA1142 NRIALDFQRG1152 NDVAFHFNPR1162 FNENNRRVIV 1172 CNTKLDNNWG1182 REERQSVFPF1192 ESGKPFKIQV1202 LVEPDHFKVA1212 VNDAHLLQYN 1222 HRVKKLNEIS1232 KLGISGDIDL1242 TSASYTMI
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| Ligand Name: 2,3,5,6-Tetrafluoro-4-Methoxy-Benzamide | Ligand Info | |||||
| Structure Description | Crystal Structure of the human galectin-3 CRD in complex with a 3'-derivative of N-Acetyllactosamine | PDB:1KJR | ||||
| Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | No | [11] |
| PDB Sequence |
PLIVPYNLPL
122 PGGVVPRMLI132 TILGTVKPNA142 NRIALDFQRG152 NDVAFHFNPR162 FNENNRRVIV 172 CNTKLDNNWG182 REERQSVFPF192 ESGKPFKIQV202 LVEPDHFKVA212 VNDAHLLQYN 222 HRVKKLNEIS232 KLGISGDIDL242 TSASYTMI
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 22 | Degree centrality | 2.36E-03 | Betweenness centrality | 3.05E-03 |
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| Closeness centrality | 2.45E-01 | Radiality | 1.43E+01 | Clustering coefficient | 6.06E-02 |
| Neighborhood connectivity | 3.87E+01 | Topological coefficient | 6.63E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TGF_beta_Receptor Signaling Pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | Hedgehog signaling events mediated by Gli proteins | |||||
| 2 | Regulation of Ras family activation | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Advanced glycosylation endproduct receptor signaling | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | Spinal Cord Injury | |||||
| 2 | AGE/RAGE pathway | |||||
| 3 | Advanced glycosylation endproduct receptor signaling | |||||
| References | Top | |||||
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| REF 1 | Therapy of experimental NASH and fibrosis with galectin inhibitors. PLoS One. 2013 Dec 18;8(12):e83481. | |||||
| REF 2 | ClinicalTrials.gov (NCT03832946) GALACTIC-1 -A Randomized, Double-blind, Multicentre, Parallel, Placebo-controlled Phase 2b Study in Subjects With Idiopathic Pulmonary Fibrosis (IPF) Investigating the Efficacy and Safety of GB0139, an Inhaled Galectin-3 Inhibitor Administered Via a Dry Powder Inhaler Over 52 Weeks. U.S.National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT02421094) Clinical Study for Non-Invasive Imaging Methods for GR-MD-02 for Treatment of Liver Fibrosis. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 6 | An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis: A Phase Ib/IIa Randomized Controlled Clinical Trial (DEFINE). Am J Respir Crit Care Med. 2023 Jan 15;207(2):138-149. | |||||
| REF 7 | Galectin-3 inhibitor GB0139 protects against acute lung injury by inhibiting neutrophil recruitment and activation. Front Pharmacol. 2022 Aug 8;13:949264. | |||||
| REF 8 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 9 | Discovery of galectin ligands in fully randomized combinatorial one-bead-one-compound (glyco)peptide libraries. Bioorg Med Chem Lett. 2007 Feb 1;17(3):793-8. | |||||
| REF 10 | Controlling Protein Conformation Through Electronic Fine-Tuning of Arginine-Arene Interactions: Synthetic, Structural, and Biological Studies | |||||
| REF 11 | Structural and thermodynamic studies on cation-Pi interactions in lectin-ligand complexes: high-affinity galectin-3 inhibitors through fine-tuning of an arginine-arene interaction. J Am Chem Soc. 2005 Feb 16;127(6):1737-43. | |||||
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