Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPPQWI0)

• DOT Name: Prostaglandin E synthase 3 (PTGES3)
• Synonyms: EC 5.3.99.3; Cytosolic prostaglandin E2 synthase; cPGES; Hsp90 co-chaperone; Progesterone receptor complex p23; Telomerase-binding protein p23
• Gene Name: PTGES3
• Related Disease:
  Cryptosporidium infection
  Advanced cancer
  Alzheimer disease
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Childhood acute lymphoblastic leukemia
  Cystic fibrosis
  Fibrosarcoma
  Hepatitis C virus infection
  Intrahepatic cholestasis of pregnancy
  Lung adenocarcinoma
  Lyme disease
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Parkinson disease
  Pervasive developmental disorder
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Schizophrenia
  Periodontitis
  Acute myelogenous leukaemia
  Adenocarcinoma
  Bone osteosarcoma
  Carcinoma
  Osteosarcoma
  Thyroid tumor
• UniProt ID: TEBP_HUMAN
• PDB ID: 1EJF; 7KRJ; 7L7I; 7L7J
• EC Number: 5.3.99.3
• Pfam ID: PF04969
• Sequence:
  MQPASAKWYDRRDYVFIEFCVEDSKDVNVNFEKSKLTFSCLGGSDNFKHLNEIDLFHCID
  PNDSKHKRTDRSILCCLRKGESGQSWPRLTKERAKLNWLSVDFNNWKDWEDDSDEDMSNF
  DRFSEMMNNMGGDEDVDLPEVDGADDDSQDSDDEKMPDLE
• Function: Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes. Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  HSF1 activation (R-HSA-3371511)
  Attenuation phase (R-HSA-3371568)
  Aryl hydrocarbon receptor signalling (R-HSA-8937144)
  ESR-mediated signaling (R-HSA-8939211)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Potential therapeutics for SARS (R-HSA-9679191)
  Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123)
• BioCyc Pathway: MetaCyc:HS03359-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cryptosporidium infection	DISLBTU2	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[7]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[8]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[9]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[10]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[11]
Intrahepatic cholestasis of pregnancy	DISMHS5F	Strong	Genetic Variation	[12]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[13]
Lyme disease	DISO70G5	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[17]
Parkinson disease	DISQVHKL	Strong	Biomarker	[18]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Altered Expression	[19]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[19]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[20]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[21]
Periodontitis	DISI9JOI	moderate	Biomarker	[22]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[23]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[24]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[25]
Carcinoma	DISH9F1N	Limited	Altered Expression	[26]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[25]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[26]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Prostaglandin E synthase 3 (PTGES3) increases the Inflammations ADR of Aspirin.	[40]
Paclitaxel	DMLB81S	Approved	Prostaglandin E synthase 3 (PTGES3) affects the response to substance of Paclitaxel.	[41]
Vinblastine	DM5TVS3	Approved	Prostaglandin E synthase 3 (PTGES3) affects the response to substance of Vinblastine.	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Prostaglandin E synthase 3 (PTGES3).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Prostaglandin E synthase 3 (PTGES3).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Prostaglandin E synthase 3 (PTGES3).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prostaglandin E synthase 3 (PTGES3).	[30]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Prostaglandin E synthase 3 (PTGES3).	[31]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Prostaglandin E synthase 3 (PTGES3).	[32]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Prostaglandin E synthase 3 (PTGES3).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Prostaglandin E synthase 3 (PTGES3).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Prostaglandin E synthase 3 (PTGES3).	[36]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Prostaglandin E synthase 3 (PTGES3).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
MG-132	DMKA2YS	Preclinical	MG-132 decreases the degradation of Prostaglandin E synthase 3 (PTGES3).	[35]
Staurosporine	DM0E9BR	Investigative	Staurosporine increases the cleavage of Prostaglandin E synthase 3 (PTGES3).	[39]
Chelerythrine	DMCP1G9	Investigative	Chelerythrine increases the cleavage of Prostaglandin E synthase 3 (PTGES3).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Prostaglandin E synthase 3 (PTGES3).	[38]

References

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