Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEUTDON)

• DME Name: Superoxide dismutase 1 (SOD1)
• Synonyms: Superoxide dismutase [Cu-Zn]; Superoxide dismutase [Copper-Zinc]; SOD1; hSod1
• Gene Name: SOD1
• UniProt ID: SODC_HUMAN
• INTEDE ID: DME0109
• Gene ID: 6647
• EC Number:
  EC: 1.15.1.1
  Oxidoreductase
  Superoxide radical acceptor oxidoreductase
  Superoxide radical acceptor oxidoreductase
  EC: 1.15.1.1
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS
  AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV
  HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
• Function: This enzyme destroys radicals which are normally produced within the cells and which are toxic to biological systems.
• KEGG Pathway:
  Amyotrophic lateral sclerosis (ALS) (hsa05014)
  Huntington's disease (hsa05016)
  Longevity regulating pathway - multiple species (hsa04213)
  Peroxisome (hsa04146)
  Prion diseases (hsa05020)
• Reactome Pathway:
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  Platelet degranulation (R-HSA-114608)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)

Molecular Interaction Atlas (MIA) of This DME

2 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[16]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[16]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	2.12E-01	2.82E-02	7.61E-02
Alopecia	ED70	Skin from scalp	1.67E-01	4.49E-02	2.22E-01
Alzheimer's disease	8A20	Entorhinal cortex	1.32E-05	-2.14E-01	-9.26E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	5.07E-02	1.94E-01	1.03E+00
Aortic stenosis	BB70	Calcified aortic valve	5.69E-01	-6.15E-01	-3.86E-01
Apnea	7A40	Hyperplastic tonsil	7.09E-01	1.72E-01	1.93E-01
Arthropathy	FA00-FA5Z	Peripheral blood	7.17E-02	-2.51E-01	-7.05E-01
Asthma	CA23	Nasal and bronchial airway	3.16E-02	9.28E-02	2.80E-01
Atopic dermatitis	EA80	Skin	9.27E-05	-1.23E-01	-1.01E+00
Autism	6A02	Whole blood	8.09E-01	1.27E-01	1.73E-01
Autoimmune uveitis	9A96	Peripheral monocyte	1.71E-02	-2.38E-01	-3.53E-01
Autosomal dominant monocytopenia	4B04	Whole blood	7.26E-01	2.30E-01	4.61E-01
Bacterial infection of gingival	1C1H	Gingival tissue	2.22E-11	-3.02E-01	-1.06E+00
Batten disease	5C56.1	Whole blood	1.00E-01	-4.19E-01	-1.77E+00
Behcet's disease	4A62	Peripheral blood	8.84E-01	6.98E-02	2.67E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.67E-01	1.24E-02	5.88E-02
Bladder cancer	2C94	Bladder tissue	1.56E-13	-4.80E-01	-8.76E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.45E-15	2.07E-01	4.81E-01
Cardioembolic stroke	8B11.20	Whole blood	6.79E-04	-1.87E-01	-9.72E-01
Cervical cancer	2C77	Cervical tissue	4.15E-03	-3.21E-01	-9.05E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	5.37E-01	-1.53E-01	-1.09E-01
Chronic hepatitis C	1E51.1	Whole blood	3.45E-01	-1.20E-01	-7.25E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	1.46E-01	-9.60E-02	-4.05E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	3.15E-01	8.74E-02	3.53E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	1.22E-01	-7.33E-01	-1.34E+00
Colon cancer	2B90	Colon tissue	4.98E-03	6.21E-02	2.69E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	7.12E-01	1.09E-01	2.20E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	9.37E-01	-4.38E-03	-2.33E-02
Endometriosis	GA10	Endometrium tissue	1.26E-01	-2.75E-01	-6.94E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	2.27E-01	-2.02E-02	-1.88E-01
Familial hypercholesterolemia	5C80.00	Whole blood	9.69E-12	7.91E-01	1.40E+00
Gastric cancer	2B72	Gastric tissue	1.12E-01	2.56E-01	1.78E+00
Glioblastopma	2A00.00	Nervous tissue	2.76E-94	-5.80E-01	-1.63E+00
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	3.88E-01	-7.37E-01	-1.08E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.24E-06	8.26E-01	2.45E+00
Head and neck cancer	2D42	Head and neck tissue	2.41E-10	-2.63E-01	-4.09E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	1.17E-01	-1.27E-01	-2.72E-01
Huntington's disease	8A01.10	Whole blood	6.39E-01	-1.48E-01	-4.47E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.19E-01	3.40E-01	1.03E+00
Immunodeficiency	4A00-4A20	Peripheral blood	1.16E-01	6.98E-02	4.52E-01
Influenza	1E30	Whole blood	2.38E-01	-2.28E-01	-2.02E+00
Interstitial cystitis	GC00.3	Bladder tissue	2.06E-05	-3.18E-01	-4.56E+00
Intracranial aneurysm	8B01.0	Intracranial artery	5.42E-03	-2.41E-01	-1.06E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	5.37E-02	-1.40E-01	-5.27E-01
Ischemic stroke	8B11	Peripheral blood	8.64E-01	-1.02E-02	-4.66E-02
Juvenile idiopathic arthritis	FA24	Peripheral blood	7.42E-14	-4.94E-01	-1.44E+00
Lateral sclerosis	8B60.4	Skin	1.08E-01	1.44E-01	1.46E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	2.51E-01	-4.92E-01	-4.33E-01
Liver cancer	2C12.0	Liver tissue	6.22E-25	-4.06E-01	-2.23E+00
Liver failure	DB99.7-DB99.8	Liver tissue	4.10E-03	-1.14E+00	-5.28E+00
Lung cancer	2C25	Lung tissue	4.80E-16	1.31E-01	5.58E-01
Lupus erythematosus	4A40	Whole blood	7.38E-01	3.03E-01	3.28E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	5.46E-01	9.58E-03	6.23E-02
Major depressive disorder	6A70-6A7Z	Whole blood	1.39E-01	-1.44E-01	-3.42E-01
Melanoma	2C30	Skin	4.59E-01	-1.10E-01	-2.97E-01
Multiple myeloma	2A83.1	Peripheral blood	7.93E-01	1.70E-02	3.89E-02
Multiple myeloma	2A83.1	Bone marrow	2.42E-06	1.57E+00	4.73E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	1.84E-01	-1.72E-01	-8.25E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	5.62E-01	1.02E-01	4.04E-01
Myelofibrosis	2A20.2	Whole blood	1.26E-01	4.45E-01	1.34E+00
Myocardial infarction	BA41-BA50	Peripheral blood	4.14E-02	-4.50E-01	-7.96E-01
Myopathy	8C70.6	Muscle tissue	4.54E-02	1.95E-01	8.84E-01
Neonatal sepsis	KA60	Whole blood	5.84E-01	-5.60E-02	-9.26E-02
Neuroectodermal tumour	2A00.11	Brain stem tissue	2.93E-03	-1.94E-01	-9.36E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	3.93E-01	1.33E-01	6.26E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	5.13E-01	-1.96E-02	-1.17E-01
Olive pollen allergy	CA08.00	Peripheral blood	6.18E-01	-6.02E-02	-5.22E-02
Oral cancer	2B6E	Oral tissue	6.49E-01	-9.49E-02	-1.85E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	7.34E-01	-8.50E-03	-1.14E-02
Osteoporosis	FB83.1	Bone marrow	5.66E-02	-2.77E-01	-2.04E+00
Ovarian cancer	2C73	Ovarian tissue	1.17E-01	-1.42E-01	-7.24E-01
Pancreatic cancer	2C10	Pancreas	2.96E-06	6.35E-01	1.83E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	7.74E-01	2.26E-02	4.46E-02
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	5.09E-01	-2.40E-03	-1.54E-02
Pituitary cancer	2D12	Pituitary tissue	2.95E-02	3.35E-01	1.05E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	5.98E-02	2.79E-01	8.17E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	2.86E-01	-2.51E-02	-1.88E-01
Polycythemia vera	2A20.4	Whole blood	1.12E-03	-2.26E-01	-6.84E-01
Pompe disease	5C51.3	Biceps muscle	4.24E-06	3.82E-01	3.13E+00
Preterm birth	KA21.4Z	Myometrium	1.42E-03	3.17E-01	2.06E+00
Prostate cancer	2C82	Prostate	9.91E-01	1.94E-02	5.83E-02
Psoriasis	EA90	Skin	1.17E-14	-1.98E-01	-1.31E+00
Rectal cancer	2B92	Rectal colon tissue	5.58E-01	-4.96E-02	-3.98E-01
Renal cancer	2C90-2C91	Kidney	4.23E-03	-3.31E-01	-9.50E-01
Retinoblastoma	2D02.2	Uvea	3.79E-04	-4.29E-01	-2.48E+00
Rheumatoid arthritis	FA20	Synovial tissue	4.17E-02	4.27E-01	8.39E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	2.25E-01	1.75E-02	1.02E-01
Schizophrenia	6A20	Prefrontal cortex	5.82E-03	-2.51E-01	-4.19E-01
Schizophrenia	6A20	Superior temporal cortex	6.53E-01	-9.27E-02	-3.58E-01
Scleroderma	4A42.Z	Whole blood	2.26E-03	-4.29E-01	-1.60E+00
Seizure	8A60-8A6Z	Whole blood	3.28E-02	8.43E-01	1.77E+00
Sensitive skin	EK0Z	Skin	4.44E-01	-2.81E-02	-2.34E-01
Sepsis with septic shock	1G41	Whole blood	4.81E-01	-2.19E-01	-4.12E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	3.14E-01	-1.59E-01	-8.02E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	8.60E-01	1.30E-01	3.37E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	9.45E-01	-7.14E-02	-2.73E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	4.82E-01	-1.74E-01	-8.01E-01
Skin cancer	2C30-2C3Z	Skin	6.67E-03	-6.24E-02	-3.34E-01
Thrombocythemia	3B63	Whole blood	3.07E-02	-5.53E-02	-1.66E-01
Thrombocytopenia	3B64	Whole blood	6.93E-01	-3.64E-03	-5.54E-03
Thyroid cancer	2D10	Thyroid	8.35E-08	-2.01E-01	-9.80E-01
Tibial muscular dystrophy	8C75	Muscle tissue	2.00E-01	-1.38E-01	-3.93E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	4.57E-05	-5.24E-01	-2.20E+01
Type 2 diabetes	5A11	Liver tissue	1.92E-01	5.12E-02	5.29E-01
Ureter cancer	2C92	Urothelium	6.27E-01	-5.48E-02	-8.10E-02
Uterine cancer	2C78	Endometrium tissue	2.17E-02	1.41E-01	2.77E-01
Vitiligo	ED63.0	Skin	9.23E-02	7.64E-05	1.24E-03

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Superoxide dismutase Cu-Zn (SOD Cu-Zn) DTT Info
• DME DTT Type: Clinical trial

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tofersen	DM0AEDT	Amyotrophic lateral sclerosis	8B60.0	Approved	[1]

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Coprexa	DMA0WEK	Neurological disorder	6B60	Phase 3	[2]
ATN-224	DMQJ5DV	Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Methoxyestradiol	DMHSL87	N. A.	N. A.	Phase 2	[3]
Midismase	DMGCRKY	Cerebral infarction	8B11.5Z	Phase 2	[4]
PC-SOD	DMUHDX3	Interstitial lung disease	CB0Z	Phase 2	[4]
Superoxide dismutase	DMSWPA6	Myocardial infarction	BA41-BA43	Phase 2	[5]
Tempol	DMUQH78	Spinal cord injury	ND51.2	Phase 2	[6]
APN-201	DMV7Q6X	Dermatitis	EA80-EA89	Phase 1/2	[7]
EUK-189	DMY9ZAS	Skin burns	ME65.0	Phase 1	[8]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AEOL-10150	DM13YRT	Multiple sclerosis	8A40	Preclinical	[9]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
EUK-207	DMLA3P1	Neurodegenerative disorder	8A20-8A23	Terminated	[10]
M-40401	DMBFCHW	Cerebrovascular ischaemia	8B1Z	Terminated	[11]
Pegorgotein	DMT819N	Head injury	NA00-NA0Z	Terminated	[12]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[13]
EC-SOD	DMYZVLN	Discovery agent	N.A.	Investigative	[14]
TDI-0060	DMXHWAY	Motor neurone disease	8B60	Investigative	[2]
TDI-0079	DM5HEIR	Motor neurone disease	8B60	Investigative	[2]
TDI-0107	DMWGDXF	Motor neurone disease	8B60	Investigative	[2]
VLTS-582	DMYH3A0	Discovery agent	N.A.	Investigative	[15]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] 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.
• [3] Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol. A superoxide dismutase inhibitor. J Biol Chem. 2003 Jan 3;278(1):407-14.
• [4] A lecithinized superoxide dismutase (PC-SOD) improves ulcerative colitis
• [5] 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.
• [6] 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.
• [7] Peyronie's disease: a critical appraisal of current diagnosis and treatment. Int J Impot Res. 2008 Sep-Oct;20(5):445-59.
• [8] Evaluation of EUK-189, a synthetic superoxide dismutase/catalase mimetic as a radiation countermeasure. Immunopharmacol Immunotoxicol. 2008;30(2):271-90.
• [9] AEOL-10150 (Aeolus). Curr Opin Investig Drugs. 2006 Jan;7(1):70-80.
• [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.
• [11] 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.
• [12] 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.
• [13] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [14] 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.
• [15] 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
• [16] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)