Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6RVLG)

• DTT Name: Superoxide dismutase Cu-Zn (SOD Cu-Zn)
• Synonyms: hSod1; Superoxide dismutase [Cu-Zn]; Superoxide dismutase 1; Superoxide dismutase
• Gene Name: SOD1
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Dissociative neurological symptom disorder [ICD-11: 6B60]
  Motor neuron disease [ICD-11: 8B60]
• BioChemical Class: Superoxide dismutase/reductase
• UniProt ID: SODC_HUMAN
• TTD ID: T22977
• EC Number: EC 1.15.1.1
• Sequence:
  MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS
  AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV
  HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
• Function: Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
• KEGG Pathway:
  Peroxisome (hsa04146)
  Amyotrophic lateral sclerosis (ALS) (hsa05014)
  Huntington's disease (hsa05016)
  Prion diseases (hsa05020)
• Reactome Pathway:
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
  Platelet degranulation (R-HSA-114608)
• BioCyc Pathway: MetaCyc:HS06899-MON

Molecular Interaction Atlas (MIA) of This DTT

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BIIB067	DM0AEDT	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[2]
Coprexa	DMA0WEK	Neurological disorder	6B60	Phase 3	[1]
ATN-224	DMQJ5DV	Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]
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], [7]
APN-201	DMV7Q6X	Dermatitis	EA80-EA89	Phase 1/2	[8]
EUK-189	DMY9ZAS	Skin burns	ME65.0	Phase 1	[9]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AEOL-10150	DM13YRT	Multiple sclerosis	8A40	Preclinical	[10]

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	[11]
M-40401	DMBFCHW	Cerebrovascular ischaemia	8B1Z	Terminated	[12]
Pegorgotein	DMT819N	Head injury	NA00-NA0Z	Terminated	[13]

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	[14]
EC-SOD	DMYZVLN	Discovery agent	N.A.	Investigative	[15]
TDI-0060	DMXHWAY	Motor neurone disease	8B60	Investigative	[1]
TDI-0079	DM5HEIR	Motor neurone disease	8B60	Investigative	[1]
TDI-0107	DMWGDXF	Motor neurone disease	8B60	Investigative	[1]
VLTS-582	DMYH3A0	Discovery agent	N.A.	Investigative	[16]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Atopic dermatitis	EA90	Skin	9.27E-05	-0.12	-1.01

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Superoxide dismutase 1 (SOD1) DME Info
• Gene Name: SOD1

2 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[17]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[17]

References

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