Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6V1ICH)

• DOT Name: Phosphoglycerate kinase 1 (PGK1)
• Synonyms: EC 2.7.2.3; Cell migration-inducing gene 10 protein; Primer recognition protein 2; PRP 2
• Gene Name: PGK1
• Related Disease:
  Adult glioblastoma
  Clear cell renal carcinoma
  Endometrial cancer
  Epithelial ovarian cancer
  Glycogen storage disease due to phosphoglycerate kinase 1 deficiency
  Matthew-Wood syndrome
  Ovarian cancer
  Ovarian neoplasm
  Renal cell carcinoma
  Advanced cancer
  Anemia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cardiac failure
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Esophageal cancer
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hemolytic anemia
  Lung cancer
  Lung carcinoma
  Melanoma
  Metastatic malignant neoplasm
  Myopathy
  Neoplasm
  Neuroblastoma
  Pancreatic cancer
  Papillary renal cell carcinoma
  Parkinson disease
  Prostate cancer
  Schizophrenia
  Stomach cancer
  Systemic lupus erythematosus
  Colorectal carcinoma
  Non-small-cell lung cancer
  Intellectual disability
  Carcinoma of liver and intrahepatic biliary tract
  Endometrial carcinoma
  Liver cancer
  Menkes disease
  Prostate carcinoma
  Rheumatoid arthritis
• UniProt ID: PGK1_HUMAN
• PDB ID: 2WZB; 2WZC; 2WZD; 2X13; 2X14; 2X15; 2XE6; 2XE7; 2XE8; 2Y3I; 2YBE; 2ZGV; 3C39; 3C3A; 3C3B; 3C3C; 3ZOZ; 4AXX; 4O33; 5M1R; 5M3U; 5M6Z; 5MXM; 5NP8; 5O7D
• EC Number: 2.7.2.3
• Pfam ID: PF00162
• Sequence:
  MSLSNKLTLDKLDVKGKRVVMRVDFNVPMKNNQITNNQRIKAAVPSIKFCLDNGAKSVVL
  MSHLGRPDGVPMPDKYSLEPVAVELKSLLGKDVLFLKDCVGPEVEKACANPAAGSVILLE
  NLRFHVEEEGKGKDASGNKVKAEPAKIEAFRASLSKLGDVYVNDAFGTAHRAHSSMVGVN
  LPQKAGGFLMKKELNYFAKALESPERPFLAILGGAKVADKIQLINNMLDKVNEMIIGGGM
  AFTFLKVLNNMEIGTSLFDEEGAKIVKDLMSKAEKNGVKITLPVDFVTADKFDENAKTGQ
  ATVASGIPAGWMGLDCGPESSKKYAEAVTRAKQIVWNGPVGVFEWEAFARGTKALMDEVV
  KATSRGCITIIGGGDTATCCAKWNTEDKVSHVSTGGGASLELLEGKVLPGVDALSNI
• Function: Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein). May play a role in sperm motility.
• Tissue Specificity: Mainly expressed in spermatogonia. Localized on the principle piece in the sperm (at protein level). Expression significantly decreased in the testis of elderly men.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  HIF-1 sig.ling pathway (hsa04066)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Manipulation of host energy metabolism (R-HSA-9636667)
  Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS02359-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Definitive	Altered Expression	[2]
Endometrial cancer	DISW0LMR	Definitive	Altered Expression	[3]
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[4]
Glycogen storage disease due to phosphoglycerate kinase 1 deficiency	DIS9MXRP	Definitive	X-linked	[5]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Definitive	Altered Expression	[4]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[4]
Renal cell carcinoma	DISQZ2X8	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[7]
Anemia	DISTVL0C	Strong	Genetic Variation	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[10]
Carcinoma	DISH9F1N	Strong	Altered Expression	[11]
Cardiac failure	DISDC067	Strong	Biomarker	[12]
Colon cancer	DISVC52G	Strong	Altered Expression	[13]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[12]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[16]
Hemolytic anemia	DIS803XQ	Strong	Genetic Variation	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Melanoma	DIS1RRCY	Strong	Altered Expression	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[9]
Myopathy	DISOWG27	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[21]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[22]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[23]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[24]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[26]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[27]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[28]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[20]
Intellectual disability	DISMBNXP	Disputed	Biomarker	[29]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[30]
Endometrial carcinoma	DISXR5CY	Limited	Altered Expression	[3]
Liver cancer	DISDE4BI	Limited	Biomarker	[30]
Menkes disease	DISJJV50	Limited	CausalMutation	[31]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[25]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phosphoglycerate kinase 1 (PGK1).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Phosphoglycerate kinase 1 (PGK1).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[39]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[41]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphoglycerate kinase 1 (PGK1).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Phosphoglycerate kinase 1 (PGK1).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Phosphoglycerate kinase 1 (PGK1).	[44]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phosphoglycerate kinase 1 (PGK1).	[46]
Marinol	DM70IK5	Approved	Marinol increases the expression of Phosphoglycerate kinase 1 (PGK1).	[47]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Phosphoglycerate kinase 1 (PGK1).	[48]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Phosphoglycerate kinase 1 (PGK1).	[49]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Phosphoglycerate kinase 1 (PGK1).	[50]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[51]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[52]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Phosphoglycerate kinase 1 (PGK1).	[53]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Phosphoglycerate kinase 1 (PGK1).	[53]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[55]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Phosphoglycerate kinase 1 (PGK1).	[56]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Phosphoglycerate kinase 1 (PGK1).	[57]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Phosphoglycerate kinase 1 (PGK1).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[59]
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[62]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphoglycerate kinase 1 (PGK1).	[63]
Clioquinol	DM746BZ	Withdrawn from market	Clioquinol increases the expression of Phosphoglycerate kinase 1 (PGK1).	[65]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[66]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[67]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[68]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Phosphoglycerate kinase 1 (PGK1).	[69]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[70]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[71]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[72]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[62]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Phosphoglycerate kinase 1 (PGK1).	[73]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Phosphoglycerate kinase 1 (PGK1).	[74]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Phosphoglycerate kinase 1 (PGK1).	[75]
	DM9CEI5		increases the expression of Phosphoglycerate kinase 1 (PGK1).	[76]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of Phosphoglycerate kinase 1 (PGK1).	[77]
Alpha-naphthoflavone	DMELOIQ	Investigative	Alpha-naphthoflavone increases the expression of Phosphoglycerate kinase 1 (PGK1).	[74]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Phosphoglycerate kinase 1 (PGK1).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Phosphoglycerate kinase 1 (PGK1).	[60]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Phosphoglycerate kinase 1 (PGK1).	[61]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Phosphoglycerate kinase 1 (PGK1).	[64]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Phosphoglycerate kinase 1 (PGK1).	[64]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Phosphoglycerate kinase 1 (PGK1).	[54]

References

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