Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ8LX4N)

• DOT Name: Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2)
• Synonyms: PEPCK-M; EC 4.1.1.32; Phosphoenolpyruvate carboxykinase 2, mitochondrial; mtPCK2
• Gene Name: PCK2
• Related Disease:
  Bone osteosarcoma
  Hyperglycemia
  Neoplasm
  Osteosarcoma
  Fatty liver disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Metabolic bone disease
  Metabolic disorder
  Non-small-cell lung cancer
  Obesity
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Type-1/2 diabetes
  Phosphoenolpyruvate carboxykinase deficiency
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Melanoma
  Phosphoenolpyruvate carboxykinase deficiency, mitochondrial
  Rectal carcinoma
• UniProt ID: PCKGM_HUMAN
• EC Number: 4.1.1.32
• Pfam ID: PF00821 ; PF17297
• Sequence:
  MAALYRPGLRLNWHGLSPLGWPSCRSIQTLRVLSGDLGQLPTGIRDFVEHSARLCQPEGI
  HICDGTEAENTATLTLLEQQGLIRKLPKYNNCWLARTDPKDVARVESKTVIVTPSQRDTV
  PLPPGGARGQLGNWMSPADFQRAVDERFPGCMQGRTMYVLPFSMGPVGSPLSRIGVQLTD
  SAYVVASMRIMTRLGTPVLQALGDGDFVKCLHSVGQPLTGQGEPVSQWPCNPEKTLIGHV
  PDQREIISFGSGYGGNSLLGKKCFALRIASRLARDEGWLAEHMLILGITSPAGKKRYVAA
  AFPSACGKTNLAMMRPALPGWKVECVGDDIAWMRFDSEGRLRAINPENGFFGVAPGTSAT
  TNPNAMATIQSNTIFTNVAETSDGGVYWEGIDQPLPPGVTVTSWLGKPWKPGDKEPCAHP
  NSRFCAPARQCPIMDPAWEAPEGVPIDAIIFGGRRPKGVPLVYEAFNWRHGVFVGSAMRS
  ESTAAAEHKGKIIMHDPFAMRPFFGYNFGHYLEHWLSMEGRKGAQLPRIFHVNWFRRDEA
  GHFLWPGFGENARVLDWICRRLEGEDSARETPIGLVPKEGALDLSGLRAIDTTQLFSLPK
  DFWEQEVRDIRSYLTEQVNQDLPKEVLAELEALERRVHKM
• Function: Mitochondrial phosphoenolpyruvate carboxykinase that catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. Can play an active role in glyceroneogenesis and gluconeogenesis.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Citrate cycle (TCA cycle) (hsa00020)
  Pyruvate metabolism (hsa00620)
  Metabolic pathways (hsa01100)
  PPAR sig.ling pathway (hsa03320)
  FoxO sig.ling pathway (hsa04068)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Insulin sig.ling pathway (hsa04910)
  Adipocytokine sig.ling pathway (hsa04920)
  Glucagon sig.ling pathway (hsa04922)
  Insulin resistance (hsa04931)
  Proximal tubule bicarbo.te reclamation (hsa04964)
• Reactome Pathway: Gluconeogenesis (R-HSA-70263)
• BioCyc Pathway: MetaCyc:HS02160-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[2]
Neoplasm	DISZKGEW	Definitive	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Metabolic bone disease	DISO7RI8	Strong	Biomarker	[8]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[9]
Obesity	DIS47Y1K	Strong	Genetic Variation	[10]
Prostate cancer	DISF190Y	Strong	Altered Expression	[11]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[11]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[11]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[12]
Phosphoenolpyruvate carboxykinase deficiency	DISOMDLN	Supportive	Autosomal recessive	[13]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[14]
Liver cancer	DISDE4BI	Limited	Altered Expression	[14]
Melanoma	DIS1RRCY	Limited	Altered Expression	[3]
Phosphoenolpyruvate carboxykinase deficiency, mitochondrial	DIS6OLCY	Limited	Autosomal recessive	[15]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[25]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[26]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[27]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[17]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[28]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[29]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[30]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[31]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[30]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[32]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[33]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[34]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[35]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[36]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[37]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[38]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[39]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[24]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[42]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[46]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[48]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[49]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[50]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[51]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[52]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[53]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2).	[43]

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