Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRM4NQY)

• DOT Name: Proepiregulin (EREG)
• Gene Name: EREG
• UniProt ID: EREG_HUMAN
• PDB ID: 1K36; 1K37; 5E8D; 5WB7; 7LEN; 7LFR; 7LFS; 8HGP
• Sequence:
  MTAGRRMEMLCAGRVPALLLCLGFHLLQAVLSTTVIPSCIPGESSDNCTALVQTEDNPRV
  AQVSITKCSSDMNGYCLHGQCIYLVDMSQNYCRCEVGYTGVRCEHFFLTVHQPLSKEYVA
  LTVILIILFLITVVGSTYYFCRWYRNRKSKEPKKEYERVTSGDPELPQV
• Function: Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation. Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation.
• Tissue Specificity: In normal adults, expressed predominantly in the placenta and peripheral blood leukocytes. High levels were detected in carcinomas of the bladder, lung, kidney and colon.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  ErbB sig.ling pathway (hsa04012)
  PI3K-Akt sig.ling pathway (hsa04151)
  Colorectal cancer (hsa05210)
• Reactome Pathway:
  Signaling by ERBB4 (R-HSA-1236394)
  SHC1 events in ERBB2 signaling (R-HSA-1250196)
  PI3K events in ERBB4 signaling (R-HSA-1250342)
  SHC1 events in ERBB4 signaling (R-HSA-1250347)
  Nuclear signaling by ERBB4 (R-HSA-1251985)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Signaling by EGFR (R-HSA-177929)
  GRB2 events in EGFR signaling (R-HSA-179812)
  GAB1 signalosome (R-HSA-180292)
  SHC1 events in EGFR signaling (R-HSA-180336)
  EGFR downregulation (R-HSA-182971)
  GRB2 events in ERBB2 signaling (R-HSA-1963640)
  PI3K events in ERBB2 signaling (R-HSA-1963642)
  EGFR interacts with phospholipase C-gamma (R-HSA-212718)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Inhibition of Signaling by Overexpressed EGFR (R-HSA-5638303)
  RAF/MAP kinase cascade (R-HSA-5673001)
  ERBB2 Regulates Cell Motility (R-HSA-6785631)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  ERBB2 Activates PTK6 Signaling (R-HSA-8847993)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Downregulation of ERBB2 signaling (R-HSA-8863795)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638)
  Signaling by ERBB2 KD Mutants (R-HSA-9664565)
  Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686)
  Signaling by ERBB2 (R-HSA-1227986)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Proepiregulin (EREG) affects the response to substance of Vinblastine.	[32]

69 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 Proepiregulin (EREG).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Proepiregulin (EREG).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Proepiregulin (EREG).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Proepiregulin (EREG).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proepiregulin (EREG).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Proepiregulin (EREG).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Proepiregulin (EREG).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Proepiregulin (EREG).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Proepiregulin (EREG).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Proepiregulin (EREG).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Proepiregulin (EREG).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Proepiregulin (EREG).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Proepiregulin (EREG).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Proepiregulin (EREG).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Proepiregulin (EREG).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Proepiregulin (EREG).	[15]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Proepiregulin (EREG).	[16]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Proepiregulin (EREG).	[17]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Proepiregulin (EREG).	[1]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Proepiregulin (EREG).	[18]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Proepiregulin (EREG).	[19]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Proepiregulin (EREG).	[1]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Proepiregulin (EREG).	[20]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Proepiregulin (EREG).	[1]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Proepiregulin (EREG).	[1]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Proepiregulin (EREG).	[1]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of Proepiregulin (EREG).	[21]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Proepiregulin (EREG).	[1]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Proepiregulin (EREG).	[1]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Proepiregulin (EREG).	[1]
Clavulanate	DM2FGRT	Approved	Clavulanate decreases the expression of Proepiregulin (EREG).	[1]
Flutamide	DMK0O7U	Approved	Flutamide increases the expression of Proepiregulin (EREG).	[1]
Amodiaquine	DME4RA8	Approved	Amodiaquine increases the expression of Proepiregulin (EREG).	[1]
Etodolac	DM6WJO9	Approved	Etodolac increases the expression of Proepiregulin (EREG).	[1]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the expression of Proepiregulin (EREG).	[1]
Zafirlukast	DMHNQOG	Approved	Zafirlukast increases the expression of Proepiregulin (EREG).	[1]
Fexofenadine	DM17ONX	Approved	Fexofenadine decreases the expression of Proepiregulin (EREG).	[1]
Entacapone	DMLBVKQ	Approved	Entacapone increases the expression of Proepiregulin (EREG).	[1]
Trazodone	DMK1GBJ	Approved	Trazodone increases the expression of Proepiregulin (EREG).	[1]
Primaquine	DMWQ16I	Approved	Primaquine increases the expression of Proepiregulin (EREG).	[1]
Bromfenac	DMKB79O	Approved	Bromfenac increases the expression of Proepiregulin (EREG).	[1]
Fludrocortisone	DMUDIR8	Approved	Fludrocortisone decreases the expression of Proepiregulin (EREG).	[1]
Phentolamine	DMXYJOB	Approved	Phentolamine decreases the expression of Proepiregulin (EREG).	[1]
Lumiracoxib	DM1S4AG	Approved	Lumiracoxib increases the expression of Proepiregulin (EREG).	[1]
Trihexyphenidyl	DMB19L8	Approved	Trihexyphenidyl increases the expression of Proepiregulin (EREG).	[1]
Procyclidine	DMHFJDT	Approved	Procyclidine increases the expression of Proepiregulin (EREG).	[1]
Penbutolol	DM4ES8F	Approved	Penbutolol increases the expression of Proepiregulin (EREG).	[1]
Phenoxybenzamine	DM8KSQH	Approved	Phenoxybenzamine decreases the expression of Proepiregulin (EREG).	[1]
Biperiden	DME78OA	Approved	Biperiden increases the expression of Proepiregulin (EREG).	[1]
Diphenhydramine	DMKQTBA	Approved	Diphenhydramine decreases the expression of Proepiregulin (EREG).	[1]
Alpidem	DMN7Y9K	Approved	Alpidem increases the expression of Proepiregulin (EREG).	[1]
Aminosalicylic acid	DMENSL5	Approved	Aminosalicylic acid increases the expression of Proepiregulin (EREG).	[1]
Pirprofen	DMMOFHT	Approved	Pirprofen increases the expression of Proepiregulin (EREG).	[1]
Protriptyline	DMNHTZI	Approved	Protriptyline increases the expression of Proepiregulin (EREG).	[1]
Minoxidil	DMA2Z4F	Approved	Minoxidil decreases the expression of Proepiregulin (EREG).	[1]
Metronidazole	DMTIVEN	Approved	Metronidazole increases the expression of Proepiregulin (EREG).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Proepiregulin (EREG).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proepiregulin (EREG).	[23]
Ticrynafen	DMLFSTR	Withdrawn from market	Ticrynafen increases the expression of Proepiregulin (EREG).	[1]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of Proepiregulin (EREG).	[1]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Proepiregulin (EREG).	[25]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Proepiregulin (EREG).	[26]
Manganese	DMKT129	Investigative	Manganese increases the expression of Proepiregulin (EREG).	[27]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Proepiregulin (EREG).	[28]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Proepiregulin (EREG).	[29]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Proepiregulin (EREG).	[30]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Proepiregulin (EREG).	[18]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate decreases the expression of Proepiregulin (EREG).	[31]
IPRONIAZIDE	DM42ENF	Investigative	IPRONIAZIDE increases the expression of Proepiregulin (EREG).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Proepiregulin (EREG).	[24]

References

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