Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG3O9BN)

• DOT Name: Cytochrome c oxidase subunit 1 (COX1)
• Synonyms: EC 7.1.1.9; Cytochrome c oxidase polypeptide I
• Gene Name: COX1
• Related Disease:
  Bladder cancer
  Mitochondrial disease
  Pediculus capitis infestation
  Schizophrenia
  Squamous cell carcinoma
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiomyopathy
  Cardiovascular disease
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Deafness
  Epithelial ovarian cancer
  Esophageal adenocarcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Idiopathic cardiomyopathy
  Lactic acidosis
  Liver cancer
  Mitochondrial myopathy
  Nasal polyp
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Parkinsonian disorder
  Plasma cell myeloma
  Prostate cancer
  Rheumatoid arthritis
  Stomach cancer
  Stroke
  Asthma
  Leber hereditary optic neuropathy
  Cytochrome-c oxidase deficiency disease
  Hereditary recurrent myoglobinuria
  MELAS syndrome
  Mitochondrial non-syndromic sensorineural hearing loss
  Cataract
  Coronary heart disease
  Leigh syndrome
  Myopathy
  OPTN-related open angle glaucoma
  Prostate carcinoma
  Undifferentiated carcinoma
• UniProt ID: COX1_HUMAN
• PDB ID: 5Z62
• EC Number: 7.1.1.9
• Pfam ID: PF00115
• Sequence:
  MFADRWLFSTNHKDIGTLYLLFGAWAGVLGTALSLLIRAELGQPGNLLGNDHIYNVIVTA
  HAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLLLLLASAMVEA
  GAGTGWTVYPPLAGNYSHPGASVDLTIFSLHLAGVSSILGAINFITTIINMKPPAMTQYQ
  TPLFVWSVLITAVLLLLSLPVLAAGITMLLTDRNLNTTFFDPAGGGDPILYQHLFWFFGH
  PEVYILILPGFGMISHIVTYYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD
  TRAYFTSATMIIAIPTGVKVFSWLATLHGSNMKWSAAVLWALGFIFLFTVGGLTGIVLAN
  SSLDIVLHDTYYVVAHFHYVLSMGAVFAIMGGFIHWFPLFSGYTLDQTYAKIHFTIMFIG
  VNLTFFPQHFLGLSGMPRRYSDYPDAYTTWNILSSVGSFISLTAVMLMIFMIWEAFASKR
  KVLMVEEPSMNLEWLYGCPPPYHTFEEPVYMKS
• Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Cardiac muscle contraction (hsa04260)
  Thermogenesis (hsa04714)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Respiratory electron transport (R-HSA-611105)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
• BioCyc Pathway: MetaCyc:HS00026-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Altered Expression	[1]
Mitochondrial disease	DISKAHA3	Definitive	Mitochondrial	[2]
Pediculus capitis infestation	DISLZYDI	Definitive	Biomarker	[3]
Schizophrenia	DISSRV2N	Definitive	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	Definitive	Altered Expression	[5]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[9]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[10]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[11]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[12]
Colon cancer	DISVC52G	Strong	Biomarker	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Deafness	DISKCLH4	Strong	Genetic Variation	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[15]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[16]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[18]
Idiopathic cardiomyopathy	DISUGBZL	Strong	Biomarker	[11]
Lactic acidosis	DISZI1ZK	Strong	Genetic Variation	[19]
Liver cancer	DISDE4BI	Strong	Biomarker	[20]
Mitochondrial myopathy	DIS9SA7V	Strong	Genetic Variation	[21]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[23]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[15]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[15]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[24]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[25]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[27]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[17]
Stroke	DISX6UHX	Strong	Biomarker	[28]
Asthma	DISW9QNS	moderate	Altered Expression	[29]
Leber hereditary optic neuropathy	DIS7Y2EE	moderate	Genetic Variation	[30]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Supportive	Autosomal recessive	[31]
Hereditary recurrent myoglobinuria	DIS4RAUG	Supportive	Autosomal dominant	[32]
MELAS syndrome	DIS81Z3S	Supportive	Mitochondrial	[33]
Mitochondrial non-syndromic sensorineural hearing loss	DISP6WS1	Supportive	Mitochondrial	[34]
Cataract	DISUD7SL	Limited	Biomarker	[35]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[36]
Leigh syndrome	DISWQU45	Limited	Mitochondrial	[2]
Myopathy	DISOWG27	Limited	Genetic Variation	[37]
OPTN-related open angle glaucoma	DISDR98A	Limited	Genetic Variation	[38]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[26]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[39]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Zidovudine	DM4KI7O	Approved	Cytochrome c oxidase subunit 1 (COX1) increases the Mitochondrial toxicity ADR of Zidovudine.	[55]
Carbachol	DMX9K8F	Approved	Cytochrome c oxidase subunit 1 (COX1) increases the Hypothalamus and pituitary gland disorders ADR of Carbachol.	[55]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cytochrome c oxidase subunit 1 (COX1).	[40]

22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[42]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[43]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[44]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[45]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[46]
Tofacitinib	DMBS370	Approved	Tofacitinib increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[47]
Nicotinamide	DMUPE07	Approved	Nicotinamide increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[44]
Zalcitabine	DMH7MUV	Approved	Zalcitabine decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[48]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[49]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[50]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[50]
Guaiacol	DMN4E7T	Phase 3	Guaiacol increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[50]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[50]
Puerarin	DMJIMXH	Phase 2	Puerarin increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[50]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[52]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[53]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[44]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[54]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid increases the expression of Cytochrome c oxidase subunit 1 (COX1).	[50]
Ethidium	DMMEQUR	Investigative	Ethidium decreases the expression of Cytochrome c oxidase subunit 1 (COX1).	[48]

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