Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZJI5FZ)

• DOT Name: Radiation-inducible immediate-early gene IEX-1 (IER3)
• Synonyms: Differentiation-dependent gene 2 protein; Protein DIF-2; Immediate early protein GLY96; Immediate early response 3 protein; PACAP-responsive gene 1 protein; Protein PRG1
• Gene Name: IER3
• Related Disease:
  Adult glioblastoma
  Crohn disease
  Glioblastoma multiforme
  Neoplasm
  Adenocarcinoma
  Advanced cancer
  Autoimmune disease
  Bladder cancer
  Bone osteosarcoma
  Cervical cancer
  Cervical carcinoma
  Colitis
  Colorectal carcinoma
  Cryohydrocytosis
  Endometriosis
  Epithelial ovarian cancer
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  High blood pressure
  Huntington disease
  Irritant contact dermatitis
  leukaemia
  Leukemia
  Lung neoplasm
  Lupus
  Matthew-Wood syndrome
  Myelodysplastic syndrome
  Myocardial infarction
  Osteoarthritis
  Osteosarcoma
  Pancreatic cancer
  Pancreatic tumour
  Pancreatitis
  Promyelocytic leukaemia
  Rheumatoid arthritis
  Severe combined immunodeficiency
  Sezary syndrome
  Skin disease
  Systemic lupus erythematosus
  Urinary bladder cancer
  Urinary bladder neoplasm
  Dilated cardiomyopathy
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Mental disorder
• UniProt ID: IEX1_HUMAN
• Sequence:
  MCHSRSCHPTMTILQAPTPAPSTIPGPRRGSGPEIFTFDPLPEPAAAPAGRPSASRGHRK
  RSRRVLYPRVVRRQLPVEEPNPAKRLLFLLLTIVFCQILMAEEGVPAPLPPEDAPNAASL
  APTPVSAVLEPFNLTSEPSDYALDLSTFLQQHPAAF
• Function: May play a role in the ERK signaling pathway by inhibiting the dephosphorylation of ERK by phosphatase PP2A-PPP2R5C holoenzyme. Acts also as an ERK downstream effector mediating survival. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment.
• Reactome Pathway: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Crohn disease	DIS2C5Q8	Definitive	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[3]
Bone osteosarcoma	DIST1004	Strong	Posttranslational Modification	[6]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[7]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[7]
Colitis	DISAF7DD	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[9]
Cryohydrocytosis	DISMQHL3	Strong	Biomarker	[10]
Endometriosis	DISX1AG8	Strong	Altered Expression	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[12]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
High blood pressure	DISY2OHH	Strong	Biomarker	[14]
Huntington disease	DISQPLA4	Strong	Biomarker	[15]
Irritant contact dermatitis	DIS62JY3	Strong	Biomarker	[16]
leukaemia	DISS7D1V	Strong	Altered Expression	[17]
Leukemia	DISNAKFL	Strong	Altered Expression	[17]
Lung neoplasm	DISVARNB	Strong	Posttranslational Modification	[4]
Lupus	DISOKJWA	Strong	Biomarker	[5]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[18]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[19]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[21]
Osteosarcoma	DISLQ7E2	Strong	Posttranslational Modification	[6]
Pancreatic cancer	DISJC981	Strong	Biomarker	[18]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[22]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[18]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[23]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[21]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Altered Expression	[24]
Sezary syndrome	DISFMTC7	Strong	Biomarker	[25]
Skin disease	DISDW8R6	Strong	Biomarker	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[27]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[3]
Dilated cardiomyopathy	DISX608J	Disputed	Biomarker	[28]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[29]
Liver cancer	DISDE4BI	Limited	Biomarker	[29]
Mental disorder	DIS3J5R8	Limited	Biomarker	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[38]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[26]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[44]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[46]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[47]
Selenium	DM25CGV	Approved	Selenium increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[48]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[49]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[44]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[50]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[51]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[52]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[53]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[54]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[55]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[56]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[57]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[58]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[59]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[60]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[61]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[62]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[62]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[63]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[33]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[64]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[65]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[66]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[67]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[62]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[68]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[69]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[70]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[71]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[72]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[51]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[73]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[74]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[75]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[62]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[76]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[42]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Radiation-inducible immediate-early gene IEX-1 (IER3).	[77]

References

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