Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT82RTMT)

• DOT Name: ]-phosphatase 1, mitochondrial (PDP1)
• Synonyms: PDP 1; EC 3.1.3.43; Protein phosphatase 2C; Pyruvate dehydrogenase phosphatase catalytic subunit 1; PDPC 1
• Gene Name: PDP1
• Related Disease:
  Acidosis
  Pyruvate dehydrogenase complex deficiency
  Subarachnoid hemorrhage
  Alzheimer disease
  Brain cancer
  Epilepsy
  Gastroenteritis
  Hepatocellular carcinoma
  Lactic acidosis
  Leigh syndrome
  Malabsorption syndrome
  Methemoglobinemia due to deficiency of methemoglobin reductase
  Neoplasm
  Paraganglioma
  Potassium-aggravated myotonia
  Prostate cancer
  Pyruvate dehydrogenase phosphatase deficiency
  leukaemia
  Leukemia
  Advanced cancer
  Fetal growth restriction
  Primary biliary cholangitis
  Prostate neoplasm
  Psychotic disorder
  Thiamine deficiency
  Tourette syndrome
• UniProt ID: PDP1_HUMAN
• EC Number: 3.1.3.43
• Pfam ID: PF00481
• Sequence:
  MPAPTQLFFPLIRNCELSRIYGTACYCHHKHLCCSSSYIPQSRLRYTPHPAYATFCRPKE
  NWWQYTQGRRYASTPQKFYLTPPQVNSILKANEYSFKVPEFDGKNVSSILGFDSNQLPAN
  APIEDRRSAATCLQTRGMLLGVFDGHAGCACSQAVSERLFYYIAVSLLPHETLLEIENAV
  ESGRALLPILQWHKHPNDYFSKEASKLYFNSLRTYWQELIDLNTGESTDIDVKEALINAF
  KRLDNDISLEAQVGDPNSFLNYLVLRVAFSGATACVAHVDGVDLHVANTGDSRAMLGVQE
  EDGSWSAVTLSNDHNAQNERELERLKLEHPKSEAKSVVKQDRLLGLLMPFRAFGDVKFKW
  SIDLQKRVIESGPDQLNDNEYTKFIPPNYHTPPYLTAEPEVTYHRLRPQDKFLVLATDGL
  WETMHRQDVVRIVGEYLTGMHHQQPIAVGGYKVTLGQMHGLLTERRTKMSSVFEDQNAAT
  HLIRHAVGNNEFGTVDHERLSKMLSLPEELARMYRDDITIIVVQFNSHVVGAYQNQE
• Function: Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA.
• Reactome Pathway: Regulation of pyruvate dehydrogenase (PDH) complex (R-HSA-204174)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acidosis	DISJQTX1	Definitive	Biomarker	[1]
Pyruvate dehydrogenase complex deficiency	DIS8RZP9	Definitive	Biomarker	[2]
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Brain cancer	DISBKFB7	Strong	Altered Expression	[5]
Epilepsy	DISBB28L	Strong	Genetic Variation	[6]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Lactic acidosis	DISZI1ZK	Strong	Genetic Variation	[9]
Leigh syndrome	DISWQU45	Strong	Biomarker	[7]
Malabsorption syndrome	DISGMUVS	Strong	Biomarker	[10]
Methemoglobinemia due to deficiency of methemoglobin reductase	DISZAEZH	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Paraganglioma	DIS2XXH5	Strong	Biomarker	[12]
Potassium-aggravated myotonia	DISRO6ZH	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[14]
Pyruvate dehydrogenase phosphatase deficiency	DISGMW2D	Strong	Autosomal recessive	[15]
leukaemia	DISS7D1V	moderate	Posttranslational Modification	[16]
Leukemia	DISNAKFL	moderate	Posttranslational Modification	[16]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[17]
Fetal growth restriction	DIS5WEJ5	Limited	Altered Expression	[2]
Primary biliary cholangitis	DIS43E0O	Limited	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[14]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[19]
Thiamine deficiency	DISONDW6	Limited	Biomarker	[20]
Tourette syndrome	DISX9D54	No Known	Unknown	[21]

2 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 ]-phosphatase 1, mitochondrial (PDP1).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of ]-phosphatase 1, mitochondrial (PDP1).	[35]

17 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 ]-phosphatase 1, mitochondrial (PDP1).	[23]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[26]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of ]-phosphatase 1, mitochondrial (PDP1).	[27]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[28]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[29]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of ]-phosphatase 1, mitochondrial (PDP1).	[30]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[31]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of ]-phosphatase 1, mitochondrial (PDP1).	[32]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[34]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[38]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of ]-phosphatase 1, mitochondrial (PDP1).	[40]

References

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