Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIAY121)

• DOT Name: Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX)
• Synonyms: COX; Coprogen oxidase; Coproporphyrinogenase; EC 1.3.3.3
• Gene Name: CPOX
• Related Disease:
  CPOX-related hereditary coproporphyria
  Acute myocardial infarction
  Adenoma
  Adult glioblastoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal adenoma
  Colorectal carcinoma
  Cytochrome-c oxidase deficiency disease
  Depression
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Harderoporphyria
  Hepatic porphyria
  Hepatocellular carcinoma
  Hereditary coproporphyria
  Leigh syndrome
  Nasopharyngeal carcinoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic ductal carcinoma
  Porphyria
  Porphyria due to ALA dehydratase deficiency
  Squamous cell carcinoma
  Type-1/2 diabetes
  Variegate porphyria
  Asthma
  Chronic obstructive pulmonary disease
  Cystic fibrosis
  Gastric cancer
  High blood pressure
  Melanoma
  Mitochondrial disease
  Prostate cancer
  Prostate carcinoma
  Acute monocytic leukemia
  Arthritis
  Cleft palate with or without ankyloglossia, X-linked
  Coronary heart disease
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Non-small-cell lung cancer
  Porphyria cutanea tarda
  Stomach cancer
• UniProt ID: HEM6_HUMAN
• PDB ID: 2AEX
• EC Number: 1.3.3.3
• Pfam ID: PF01218
• Sequence:
  MALQLGRLSSGPCWLVARGGCGGPRAWSQCGGGGLRAWSQRSAAGRVCRPPGPAGTEQSR
  GLGHGSTSRGGPWVGTGLAAALAGLVGLATAAFGHVQRAEMLPKTSGTRATSLGRPEEEE
  DELAHRCSSFMAPPVTDLGELRRRPGDMKTKMELLILETQAQVCQALAQVDGGANFSVDR
  WERKEGGGGISCVLQDGCVFEKAGVSISVVHGNLSEEAAKQMRSRGKVLKTKDGKLPFCA
  MGVSSVIHPKNPHAPTIHFNYRYFEVEEADGNKQWWFGGGCDLTPTYLNQEDAVHFHRTL
  KEACDQHGPDLYPKFKKWCDDYFFIAHRGERRGIGGIFFDDLDSPSKEEVFRFVQSCARA
  VVPSYIPLVKKHCDDSFTPQEKLWQQLRRGRYVEFNLLYDRGTKFGLFTPGSRIESILMS
  LPLTARWEYMHSPSENSKEAEILEVLRHPRDWVR
• Function: Catalyzes the aerobic oxidative decarboxylation of propionate groups of rings A and B of coproporphyrinogen-III to yield the vinyl groups in protoporphyrinogen-IX and participates to the sixth step in the heme biosynthetic pathway.
• KEGG Pathway:
  Porphyrin metabolism (hsa00860)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Heme biosynthesis (R-HSA-189451)
• BioCyc Pathway: MetaCyc:HS01369-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

52 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
CPOX-related hereditary coproporphyria	DISKRUWP	Definitive	Semidominant	[1]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[2]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[10]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Biomarker	[11]
Depression	DIS3XJ69	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[15]
Harderoporphyria	DIS8I5LT	Strong	Autosomal recessive	[16]
Hepatic porphyria	DISMI8EV	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[18]
Hereditary coproporphyria	DISDXYP2	Strong	Autosomal dominant	[16]
Leigh syndrome	DISWQU45	Strong	Genetic Variation	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[13]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[13]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[22]
Porphyria	DIS9YL4C	Strong	Genetic Variation	[23]
Porphyria due to ALA dehydratase deficiency	DIS3EXTY	Strong	Altered Expression	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[26]
Variegate porphyria	DIS8OK5W	Strong	Biomarker	[27]
Asthma	DISW9QNS	moderate	Altered Expression	[28]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[29]
Cystic fibrosis	DIS2OK1Q	moderate	Biomarker	[30]
Gastric cancer	DISXGOUK	moderate	Biomarker	[31]
High blood pressure	DISY2OHH	moderate	Biomarker	[32]
Melanoma	DIS1RRCY	moderate	Biomarker	[33]
Mitochondrial disease	DISKAHA3	moderate	Biomarker	[34]
Prostate cancer	DISF190Y	moderate	Biomarker	[35]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[35]
Acute monocytic leukemia	DIS28NEL	Limited	Biomarker	[36]
Arthritis	DIST1YEL	Limited	Biomarker	[37]
Cleft palate with or without ankyloglossia, X-linked	DISARMUU	Limited	Genetic Variation	[38]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[39]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[40]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[40]
Major depressive disorder	DIS4CL3X	Limited	Biomarker	[41]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[42]
Porphyria cutanea tarda	DISHNFD7	Limited	Biomarker	[43]
Stomach cancer	DISKIJSX	Limited	Biomarker	[31]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Heme	DMGC287	Investigative	Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX) increases the chemical synthesis of Heme.	[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 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[45]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[46]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[47]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[48]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[49]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[50]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX).	[54]

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