Details of Drug Off-Target (DOT)

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

• DOT Name: NADH-ubiquinone oxidoreductase chain 1 (ND1)
• Synonyms: EC 7.1.1.2; NADH dehydrogenase subunit 1
• Gene Name: ND1
• Related Disease:
  Intellectual disability
  Leber hereditary optic neuropathy
  Leigh syndrome
  Mitochondrial disease
  Advanced cancer
  Alzheimer disease
  Bipolar disorder
  Colorectal carcinoma
  Dystonia
  Frontotemporal dementia
  Hepatocellular carcinoma
  LennoxGastaut syndrome
  Long QT syndrome
  Multiple sclerosis
  Non-insulin dependent diabetes
  Osteoarthritis
  Parkinson disease
  Pathologic nystagmus
  Rheumatoid arthritis
  Schizophrenia
  Thyroid gland carcinoma
  Type-1/2 diabetes
  Bone osteosarcoma
  Cardiomyopathy
  High blood pressure
  Keratoconus
  Obesity
  Osteosarcoma
  Peripheral sensory neuropathies
  Maternally-inherited Leigh syndrome
  MELAS syndrome
  Mitochondrial complex I deficiency
  Hypertrophic cardiomyopathy
  Lactic acidosis
  Optic nerve disorder
  Spinocerebellar ataxia type 3
  West syndrome
• UniProt ID: NU1M_HUMAN
• PDB ID: 5XTC; 5XTD
• EC Number: 7.1.1.2
• Pfam ID: PF00146
• Sequence:
  MPMANLLLLIVPILIAMAFLMLTERKILGYMQLRKGPNVVGPYGLLQPFADAMKLFTKEP
  LKPATSTITLYITAPTLALTIALLLWTPLPMPNPLVNLNLGLLFILATSSLAVYSILWSG
  WASNSNYALIGALRAVAQTISYEVTLAIILLSTLLMSGSFNLSTLITTQEHLWLLLPSWP
  LAMMWFISTLAETNRTPFDLAEGESELVSGFNIEYAAGPFALFFMAEYTNIIMMNTLTTT
  IFLGTTYDALSPELYTTYFVTKTLLLTSLFLWIRTAYPRFRYDQLMHLLWKNFLPLTLAL
  LMWYVSMPITISSIPPQT
• Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
  Retrograde endocan.binoid sig.ling (hsa04723)
  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:
  Complex I biogenesis (R-HSA-6799198)
  Respiratory electron transport (R-HSA-611105)
• BioCyc Pathway: MetaCyc:HS00030-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Altered Expression	[1]
Leber hereditary optic neuropathy	DIS7Y2EE	Definitive	Mitochondrial	[2]
Leigh syndrome	DISWQU45	Definitive	Mitochondrial	[3]
Mitochondrial disease	DISKAHA3	Definitive	Mitochondrial	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[5]
Bipolar disorder	DISAM7J2	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Dystonia	DISJLFGW	Strong	Genetic Variation	[8]
Frontotemporal dementia	DISKYHXL	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
LennoxGastaut syndrome	DISOTGO5	Strong	Genetic Variation	[10]
Long QT syndrome	DISMKWS3	Strong	Genetic Variation	[11]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[12]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[13]
Osteoarthritis	DIS05URM	Strong	Biomarker	[14]
Parkinson disease	DISQVHKL	Strong	Biomarker	[15]
Pathologic nystagmus	DIS1QSPO	Strong	Biomarker	[16]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[14]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[17]
Thyroid gland carcinoma	DISMNGZ0	Strong	Genetic Variation	[18]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[19]
Bone osteosarcoma	DIST1004	moderate	Genetic Variation	[20]
Cardiomyopathy	DISUPZRG	moderate	Genetic Variation	[21]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[22]
Keratoconus	DISOONXH	moderate	Altered Expression	[23]
Obesity	DIS47Y1K	moderate	Biomarker	[24]
Osteosarcoma	DISLQ7E2	moderate	Genetic Variation	[20]
Peripheral sensory neuropathies	DISYWI6M	moderate	Genetic Variation	[25]
Maternally-inherited Leigh syndrome	DISGE06V	Supportive	Mitochondrial	[26]
MELAS syndrome	DIS81Z3S	Supportive	Mitochondrial	[27]
Mitochondrial complex I deficiency	DIS13M7V	Supportive	Autosomal recessive	[28]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Genetic Variation	[21]
Lactic acidosis	DISZI1ZK	Limited	Genetic Variation	[29]
Optic nerve disorder	DISSOQM8	Limited	Genetic Variation	[30]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Biomarker	[31]
West syndrome	DISLIAU9	Limited	Genetic Variation	[32]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Capsaicin	DMGMF6V	Approved	NADH-ubiquinone oxidoreductase chain 1 (ND1) increases the response to substance of Capsaicin.	[45]
Haloperidol	DM96SE0	Approved	NADH-ubiquinone oxidoreductase chain 1 (ND1) increases the Parkinsonism ADR of Haloperidol.	[46]
Thiothixene	DMDINC4	Approved	NADH-ubiquinone oxidoreductase chain 1 (ND1) increases the Parkinsonism ADR of Thiothixene.	[46]
Chlorpromazine	DMBGZI3	Phase 3 Trial	NADH-ubiquinone oxidoreductase chain 1 (ND1) increases the Parkinsonism ADR of Chlorpromazine.	[46]

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 NADH-ubiquinone oxidoreductase chain 1 (ND1).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[35]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[36]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[37]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol decreases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[38]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[39]
INX-189	DMSTJ6Q	Phase 2	INX-189 decreases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[40]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[42]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[43]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[44]
Ethidium	DMMEQUR	Investigative	Ethidium decreases the expression of NADH-ubiquinone oxidoreductase chain 1 (ND1).	[38]

References

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