Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGEU8IK)

• DOT Name: Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1)
• Synonyms: EC 1.2.4.1; PDHE1-A type I
• Gene Name: PDHA1
• Related Disease:
  Leigh syndrome
  Pyruvate dehydrogenase complex deficiency
  Pyruvate dehydrogenase E1-alpha deficiency
  Advanced cancer
  Carcinoma of esophagus
  Cerebellar ataxia
  Cerebral palsy
  Cholangiocarcinoma
  Chromosomal disorder
  Coffin-Lowry syndrome
  Dystonia
  Epilepsy
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Inborn error of metabolism
  Mitochondrial disease
  Myocardial ischemia
  Neoplasm
  Neoplasm of esophagus
  Prostate cancer
  West syndrome
  Arthrogryposis
  Carcinoma
  Fetal akinesia deformation sequence 1
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lactic acidosis
  Movement disorder
  Prostate carcinoma
  Obsolete Leigh syndrome with leukodystrophy
  Gastric cancer
  Lewy body dementia
  Osteoarthritis
  Parkinson disease
  Prostate neoplasm
  Stomach cancer
• UniProt ID: ODPA_HUMAN
• PDB ID: 1NI4; 2OZL; 3EXE; 3EXF; 3EXG; 3EXH; 3EXI; 6CER; 6CFO
• EC Number: 1.2.4.1
• Pfam ID: PF00676
• Sequence:
  MRKMLAAVSRVLSGASQKPASRVLVASRNFANDATFEIKKCDLHRLEEGPPVTTVLTRED
  GLKYYRMMQTVRRMELKADQLYKQKIIRGFCHLCDGQEACCVGLEAGINPTDHLITAYRA
  HGFTFTRGLSVREILAELTGRKGGCAKGKGGSMHMYAKNFYGGNGIVGAQVPLGAGIALA
  CKYNGKDEVCLTLYGDGAANQGQIFEAYNMAALWKLPCIFICENNRYGMGTSVERAAAST
  DYYKRGDFIPGLRVDGMDILCVREATRFAAAYCRSGKGPILMELQTYRYHGHSMSDPGVS
  YRTREEIQEVRSKSDPIMLLKDRMVNSNLASVEELKEIDVEVRKEIEDAAQFATADPEPP
  LEELGYHIYSSDPPFEVRGANQWIKFKSVS
• Function: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Citrate cycle (TCA cycle) (hsa00020)
  Pyruvate metabolism (hsa00620)
  Lipoic acid metabolism (hsa00785)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  2-Oxocarboxylic acid metabolism (hsa01210)
  HIF-1 sig.ling pathway (hsa04066)
  Glucagon sig.ling pathway (hsa04922)
  Central carbon metabolism in cancer (hsa05230)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)
  Signaling by Retinoic Acid (R-HSA-5362517)
  Pyruvate metabolism (R-HSA-70268)
  Regulation of pyruvate dehydrogenase (PDH) complex (R-HSA-204174)
• BioCyc Pathway: MetaCyc:HS05573-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leigh syndrome	DISWQU45	Definitive	X-linked	[1]
Pyruvate dehydrogenase complex deficiency	DIS8RZP9	Definitive	Biomarker	[2]
Pyruvate dehydrogenase E1-alpha deficiency	DISZ6WMJ	Definitive	X-linked	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[6]
Cerebral palsy	DIS82ODL	Strong	Biomarker	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[8]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[9]
Coffin-Lowry syndrome	DISMTBDA	Strong	Genetic Variation	[10]
Dystonia	DISJLFGW	Strong	Biomarker	[11]
Epilepsy	DISBB28L	Strong	Biomarker	[2]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[5]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[12]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[12]
Inborn error of metabolism	DISO5FAY	Strong	Genetic Variation	[13]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[14]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[16]
West syndrome	DISLIAU9	Strong	Genetic Variation	[14]
Arthrogryposis	DISC81CM	moderate	Genetic Variation	[17]
Carcinoma	DISH9F1N	moderate	Altered Expression	[18]
Fetal akinesia deformation sequence 1	DISKDI9L	moderate	Genetic Variation	[17]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[19]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[20]
Lactic acidosis	DISZI1ZK	moderate	Genetic Variation	[21]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[22]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[16]
Obsolete Leigh syndrome with leukodystrophy	DISABU9D	Supportive	Autosomal recessive	[23]
Gastric cancer	DISXGOUK	Limited	Biomarker	[24]
Lewy body dementia	DISAE66J	Limited	Biomarker	[25]
Osteoarthritis	DIS05URM	Limited	Biomarker	[26]
Parkinson disease	DISQVHKL	Limited	Biomarker	[25]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[16]
Stomach cancer	DISKIJSX	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[31]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[33]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[34]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[35]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[36]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[37]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[38]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[42]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[43]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[44]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[45]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[40]
AZD-7545	DMU6L4I	Terminated	AZD-7545 decreases the phosphorylation of Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1).	[41]

References

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