Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRODL0T)

• DOT Name: Gamma-enolase (ENO2)
• Synonyms: EC 4.2.1.11; 2-phospho-D-glycerate hydro-lyase; Enolase 2; Neural enolase; Neuron-specific enolase; NSE
• Gene Name: ENO2
• Related Disease:
  Breast carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Toxic shock syndrome
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Breast cancer
  Childhood acute lymphoblastic leukemia
  Clear cell renal carcinoma
  Encephalitis
  Hyperglycemia
  Lewy body dementia
  Lyme disease
  Lymphoma
  Nervous system disease
  Non-small-cell lung cancer
  Parkinson disease
  Parkinsonian disorder
  Primitive neuroectodermal tumor
  Prostate cancer
  Small-cell lung cancer
  Squamous cell carcinoma
  Temporal lobe epilepsy
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Carcinoma
  Ewing sarcoma/peripheral primitive neuroectodermal tumor
  Metastatic malignant neoplasm
  Neurodegeneration with brain iron accumulation 5
  Schizophrenia
  Creutzfeldt Jacob disease
  Adult lymphoma
  Advanced cancer
  Cardiac arrest
  Pediatric lymphoma
  Prostate carcinoma
  Pulmonary disease
• UniProt ID: ENOG_HUMAN
• PDB ID: 1TE6; 2AKM; 2AKZ; 3UCC; 3UCD; 3UJE; 3UJF; 3UJR; 3UJS; 4ZA0; 4ZCW; 5EU9; 5IDZ; 5TD9; 5TIJ; 7MBH
• EC Number: 4.2.1.11
• Pfam ID: PF00113 ; PF03952
• Sequence:
  MSIEKIWAREILDSRGNPTVEVDLYTAKGLFRAAVPSGASTGIYEALELRDGDKQRYLGK
  GVLKAVDHINSTIAPALISSGLSVVEQEKLDNLMLELDGTENKSKFGANAILGVSLAVCK
  AGAAERELPLYRHIAQLAGNSDLILPVPAFNVINGGSHAGNKLAMQEFMILPVGAESFRD
  AMRLGAEVYHTLKGVIKDKYGKDATNVGDEGGFAPNILENSEALELVKEAIDKAGYTEKI
  VIGMDVAASEFYRDGKYDLDFKSPTDPSRYITGDQLGALYQDFVRDYPVVSIEDPFDQDD
  WAAWSKFTANVGIQIVGDDLTVTNPKRIERAVEEKACNCLLLKVNQIGSVTEAIQACKLA
  QENGWGVMVSHRSGETEDTFIADLVVGLCTGQIKTGAPCRSERLAKYNQLMRIEEELGDE
  ARFAGHNFRNPSVL
• Function: Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival.
• Tissue Specificity: The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  R. degradation (hsa03018)
  HIF-1 sig.ling pathway (hsa04066)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS10646-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[2]
Lung cancer	DISCM4YA	Definitive	Biomarker	[3]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[3]
Lung neoplasm	DISVARNB	Definitive	Biomarker	[4]
Toxic shock syndrome	DISX5S53	Definitive	Biomarker	[5]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[6]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[7]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[9]
Encephalitis	DISLD1RL	Strong	Biomarker	[10]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[11]
Lewy body dementia	DISAE66J	Strong	Biomarker	[12]
Lyme disease	DISO70G5	Strong	Biomarker	[13]
Lymphoma	DISN6V4S	Strong	Biomarker	[14]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[15]
Parkinson disease	DISQVHKL	Strong	Biomarker	[12]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[16]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[19]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[20]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[21]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[23]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[23]
Carcinoma	DISH9F1N	moderate	Biomarker	[24]
Ewing sarcoma/peripheral primitive neuroectodermal tumor	DISD4VQC	moderate	Altered Expression	[25]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[26]
Neurodegeneration with brain iron accumulation 5	DISW9SFJ	moderate	Biomarker	[27]
Schizophrenia	DISSRV2N	moderate	Biomarker	[28]
Creutzfeldt Jacob disease	DISCB6RX	Disputed	Altered Expression	[29]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[30]
Cardiac arrest	DIS9DIA4	Limited	Biomarker	[31]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[18]
Pulmonary disease	DIS6060I	Limited	Biomarker	[32]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Gamma-enolase (ENO2) decreases the response to substance of Methotrexate.	[72]

45 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 Gamma-enolase (ENO2).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Gamma-enolase (ENO2).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Gamma-enolase (ENO2).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Gamma-enolase (ENO2).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Gamma-enolase (ENO2).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Gamma-enolase (ENO2).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Gamma-enolase (ENO2).	[39]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Gamma-enolase (ENO2).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Gamma-enolase (ENO2).	[41]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Gamma-enolase (ENO2).	[42]
Selenium	DM25CGV	Approved	Selenium increases the expression of Gamma-enolase (ENO2).	[43]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Gamma-enolase (ENO2).	[44]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Gamma-enolase (ENO2).	[45]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Gamma-enolase (ENO2).	[38]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Gamma-enolase (ENO2).	[46]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Gamma-enolase (ENO2).	[47]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Gamma-enolase (ENO2).	[37]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Gamma-enolase (ENO2).	[48]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Gamma-enolase (ENO2).	[37]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Gamma-enolase (ENO2).	[37]
Estrone	DM5T6US	Approved	Estrone decreases the expression of Gamma-enolase (ENO2).	[38]
Estriol	DMOEM2I	Approved	Estriol decreases the expression of Gamma-enolase (ENO2).	[38]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Gamma-enolase (ENO2).	[49]
LY2835219	DM93VBZ	Approved	LY2835219 increases the expression of Gamma-enolase (ENO2).	[50]
Aluminium	DM6ECN9	Approved	Aluminium decreases the activity of Gamma-enolase (ENO2).	[51]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Gamma-enolase (ENO2).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Gamma-enolase (ENO2).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Gamma-enolase (ENO2).	[54]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Gamma-enolase (ENO2).	[38]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Gamma-enolase (ENO2).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Gamma-enolase (ENO2).	[55]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Gamma-enolase (ENO2).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Gamma-enolase (ENO2).	[57]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Gamma-enolase (ENO2).	[59]
WIN-55212-2	DMACBIW	Terminated	WIN-55212-2 decreases the expression of Gamma-enolase (ENO2).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Gamma-enolase (ENO2).	[61]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Gamma-enolase (ENO2).	[62]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Gamma-enolase (ENO2).	[63]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Gamma-enolase (ENO2).	[64]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Gamma-enolase (ENO2).	[65]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Gamma-enolase (ENO2).	[66]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Gamma-enolase (ENO2).	[68]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Gamma-enolase (ENO2).	[69]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Gamma-enolase (ENO2).	[70]
methylglyoxal	DMRC3OZ	Investigative	methylglyoxal decreases the expression of Gamma-enolase (ENO2).	[71]

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 affects the phosphorylation of Gamma-enolase (ENO2).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
D-glucose	DMMG2TO	Investigative	D-glucose increases the secretion of Gamma-enolase (ENO2).	[67]

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