Target Information
| Target General Information | Top | |||||
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| Target ID |
T22977
(Former ID: TTDR00265)
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| Target Name |
Superoxide dismutase Cu-Zn (SOD Cu-Zn)
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| Synonyms |
hSod1; Superoxide dismutase [Cu-Zn]; Superoxide dismutase 1; Superoxide dismutase
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| Gene Name |
SOD1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Dissociative neurological symptom disorder [ICD-11: 6B60] | |||||
| Function |
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
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| BioChemical Class |
Superoxide dismutase/reductase
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| UniProt ID | ||||||
| EC Number |
EC 1.15.1.1
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| Sequence |
MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS
AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A03234 ; BADD_A03633 ; BADD_A04153 ; BADD_A04623 ; BADD_A06020 | |||||
| HIT2.0 ID | T30D9G | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | Coprexa | Drug Info | Phase 3 | Neurological disorder | [1] | |
| 2 | ATN-224 | Drug Info | Phase 2 | Solid tumour/cancer | [3] | |
| 3 | Midismase | Drug Info | Phase 2 | Cerebral infarction | [4] | |
| 4 | Superoxide dismutase | Drug Info | Phase 2 | Myocardial infarction | [5] | |
| 5 | Tempol | Drug Info | Phase 2 | Spinal cord injury | [6] | |
| 6 | APN-201 | Drug Info | Phase 1/2 | Dermatitis | [7] | |
| 7 | EUK-189 | Drug Info | Phase 1 | Skin burns | [8] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | AEOL-10150 | Drug Info | Preclinical | Multiple sclerosis | [9] | |
| Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
| 1 | EUK-207 | Drug Info | Terminated | Neurodegenerative disorder | [10] | |
| 2 | M-40401 | Drug Info | Terminated | Cerebrovascular ischaemia | [11] | |
| 3 | Pegorgotein | Drug Info | Terminated | Head injury | [12] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | Coprexa | Drug Info | [1] | |||
| 2 | ATN-224 | Drug Info | [1] | |||
| 3 | Methoxyestradiol | Drug Info | [13] | |||
| 4 | Acetate Ion | Drug Info | [22] | |||
| Modulator | [+] 13 Modulator drugs | + | ||||
| 1 | Midismase | Drug Info | [14] | |||
| 2 | Superoxide dismutase | Drug Info | [15] | |||
| 3 | Tempol | Drug Info | [16], [17] | |||
| 4 | APN-201 | Drug Info | [18] | |||
| 5 | EUK-189 | Drug Info | [8] | |||
| 6 | AEOL-10150 | Drug Info | [19] | |||
| 7 | EUK-207 | Drug Info | [10] | |||
| 8 | M-40401 | Drug Info | [20] | |||
| 9 | Pegorgotein | Drug Info | [21] | |||
| 10 | EC-SOD | Drug Info | [23] | |||
| 11 | TDI-0060 | Drug Info | [1] | |||
| 12 | TDI-0079 | Drug Info | [1] | |||
| 13 | VLTS-582 | Drug Info | [24] | |||
| 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: Epinephrine | Ligand Info | |||||
| Structure Description | Structure of human I113T SOD1 complexed with adrenaline in the p21 space group. | PDB:4A7U | ||||
| Method | X-ray diffraction | Resolution | 0.98 Å | Mutation | Yes | [25] |
| PDB Sequence |
ATKAVCVLKG
10 DGPVQGIINF20 EQKESNGPVK30 VWGSIKGLTE40 GLHGFHVHEF50 GDNTAGCTSA 60 GPHFNPLSRK70 HGGPKDEERH80 VGDLGNVTAD90 KDGVADVSIE100 DSVISLSGDH 110 CITGRTLVVH120 EKADDLGKGG130 NEESTKTGNA140 GSRLACGVIG150 IAQ |
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| Ligand Name: Dopamine | Ligand Info | |||||
| Structure Description | Structure of human I113T SOD1 mutant complexed with dopamine in the p21 space group | PDB:4A7V | ||||
| Method | X-ray diffraction | Resolution | 1.00 Å | Mutation | Yes | [25] |
| PDB Sequence |
ATKAVCVLKG
10 DGPVQGIINF20 EQKESNGPVK30 VWGSIKGLTE40 GLHGFHVHEF50 GDNTAGCTSA 60 GPHFNPLSRK70 HGGPKDEERH80 VGDLGNVTAD90 KDGVADVSIE100 DSVISLSGDH 110 CITGRTLVVH120 EKADDLGKGG130 NEESTKTGNA140 GSRLACGVIG150 IAQ |
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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).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Peroxisome | hsa04146 | Affiliated Target |
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| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| Longevity regulating pathway - multiple species | hsa04213 | Affiliated Target |
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| Class: Organismal Systems => Aging | Pathway Hierarchy | ||
| Degree | 20 | Degree centrality | 2.15E-03 | Betweenness centrality | 3.13E-03 |
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| Closeness centrality | 2.42E-01 | Radiality | 1.42E+01 | Clustering coefficient | 7.89E-02 |
| Neighborhood connectivity | 2.48E+01 | Topological coefficient | 6.60E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| 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-regulating Transcription Factors | ||||||
| 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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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | Reactive oxygen species degradation | |||||
| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Peroxisome | |||||
| 2 | Amyotrophic lateral sclerosis (ALS) | |||||
| 3 | Huntington's disease | |||||
| 4 | Prion diseases | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Degradation of Superoxides | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | Validated nuclear estrogen receptor alpha network | |||||
| 2 | FOXA1 transcription factor network | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Platelet degranulation | |||||
| 2 | Detoxification of Reactive Oxygen Species | |||||
| WikiPathways | [+] 10 WikiPathways | + | ||||
| 1 | Oxidative Stress | |||||
| 2 | Copper homeostasis | |||||
| 3 | Detoxification of Reactive Oxygen Species | |||||
| 4 | Nifedipine Activity | |||||
| 5 | Amyotrophic lateral sclerosis (ALS) | |||||
| 6 | Dopamine metabolism | |||||
| 7 | AGE/RAGE pathway | |||||
| 8 | Folate Metabolism | |||||
| 9 | Vitamin B12 Metabolism | |||||
| 10 | Selenium Micronutrient Network | |||||
| References | Top | |||||
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| REF 1 | Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1. Clin Cancer Res. 2006 Aug 15;12(16):4974-82. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032052) | |||||
| REF 3 | ClinicalTrials.gov (NCT00405574) Study of ATN-224 in Patients With Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT00685763) Proton Therapy for Unresectable Cancer (CA) of Pancreas. U.S. National Institutes of Health. | |||||
| REF 5 | Phase II trial of copper zinc superoxide dismutase (CuZn SOD) in the treatment of Crohn's disease. Free Radic Res Commun. 1991;12-13 Pt 2:563-9. | |||||
| REF 6 | ClinicalTrials.gov (NCT00801086) Efficacy Study of Tempol to Prevent Hair Loss From Radiotherapy to the Brain. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT01513278) Study of APN201 (Liposomal Recombinant Human Cu/Zn-Superoxide Dismutase) for the Prevention of Radiation-induced Dermatitis in Women With Breast Cancer. U.S. NationalInstitutes of Health. | |||||
| REF 8 | Evaluation of EUK-189, a synthetic superoxide dismutase/catalase mimetic as a radiation countermeasure. Immunopharmacol Immunotoxicol. 2008;30(2):271-90. | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013050) | |||||
| REF 10 | A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin. J Invest Dermatol. 2013 Apr;133(4):1088-96. | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018067) | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005631) | |||||
| REF 13 | Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol. A superoxide dismutase inhibitor. J Biol Chem. 2003 Jan 3;278(1):407-14. | |||||
| REF 14 | A lecithinized superoxide dismutase (PC-SOD) improves ulcerative colitis | |||||
| REF 15 | Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase: a novel biotechnology-based blood substitute that transports both oxygen and carbon dioxide and also acts as an antioxidant.Artif Cells Blood Substit Immobil Biotechnol.2011 Jun;39(3):127-36. | |||||
| REF 16 | The superoxide dismutase mimetic, tempol, reduces the bioavailability of nitric oxide and does not alter L-NAME-induced hypertension in rats. Basic Clin Pharmacol Toxicol. 2005 Jul;97(1):29-34. | |||||
| REF 17 | Effect of the addition of two superoxide dismutase analogues (Tempo and Tempol) to alpaca semen extender for cryopreservation. Theriogenology. 2013 Mar 15;79(5):842-6. | |||||
| REF 18 | Peyronie's disease: a critical appraisal of current diagnosis and treatment. Int J Impot Res. 2008 Sep-Oct;20(5):445-59. | |||||
| REF 19 | AEOL-10150 (Aeolus). Curr Opin Investig Drugs. 2006 Jan;7(1):70-80. | |||||
| REF 20 | Protective effects of a new stable, highly active SOD mimetic, M40401 in splanchnic artery occlusion and reperfusion. Br J Pharmacol. 2001 Jan;132(1):19-29. | |||||
| REF 21 | Clinical trials with Dismutec (pegorgotein; polyethylene glycol-conjugated superoxide dismutase; PEG-SOD) in the treatment of severe closed head injury. Adv Exp Med Biol. 1994;366:389-400. | |||||
| REF 22 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 23 | Extracellular superoxide dismutase (ecSOD) in vascular biology: an update on exogenous gene transfer and endogenous regulators of ecSOD.Transl Res.2008 Feb;151(2):68-78. | |||||
| REF 24 | A Phase I Study of Concurrent Chemotherapy (Paclitaxel and Carboplatin) and Thoracic Radiotherapy with Swallowed Manganese Superoxide Dismutase Plasmid Liposome Protection in Patients with Locally Advanced Stage III Non-Small-Cell Lung Cancer | |||||
| REF 25 | Ligand binding and aggregation of pathogenic SOD1. Nat Commun. 2013;4:1758. | |||||
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