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]
• 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

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	[2]

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	[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]
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	[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	[15]

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	Adenocarcinoma	2D40	Approved	[16]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[16]

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] 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)