Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRHJ8HK)

• DOT Name: Protein CREG1 (CREG1)
• Synonyms: Cellular repressor of E1A-stimulated genes 1
• Gene Name: CREG1
• Related Disease:
  Acute myocardial infarction
  Adult teratoma
  Arrhythmia
  Arteriosclerosis
  Atherosclerosis
  Endometrial carcinoma
  Fatty liver disease
  Metabolic disorder
  Obesity
  Prostate cancer
  Prostate neoplasm
  Teratoma
  Vascular disease
  Ankylosing spondylitis
  Cardiovascular disease
  Myocardial ischemia
  Recessive X-linked ichthyosis
  Fibrosarcoma
  Li-Fraumeni syndrome
  Coronary atherosclerosis
  Myocardial infarction
  Neoplasm
  Rheumatoid arthritis
• UniProt ID: CREG1_HUMAN
• PDB ID: 1XHN
• Pfam ID: PF13883
• Sequence:
  MAGLSRGSARALLAALLASTLLALLVSPARGRGGRDHGDWDEASRLPPLPPREDAARVAR
  FVTHVSDWGALATISTLEAVRGRPFADVLSLSDGPPGAGSGVPYFYLSPLQLSVSNLQEN
  PYATLTMTLAQTNFCKKHGFDPQSPLCVHIMLSGTVTKVNETEMDIAKHSLFIRHPEMKT
  WPSSHNWFFAKLNITNIWVLDYFGGPKIVTPEEYYNVTVQ
• Function: May contribute to the transcriptional control of cell growth and differentiation. Antagonizes transcriptional activation and cellular transformation by the adenovirus E1A protein. The transcriptional control activity of cell growth requires interaction with IGF2R.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Adult teratoma	DISBY81U	Strong	Biomarker	[1]
Arrhythmia	DISFF2NI	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[3]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[4]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[6]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[6]
Teratoma	DIS6ICY4	Strong	Biomarker	[1]
Vascular disease	DISVS67S	Strong	Biomarker	[7]
Ankylosing spondylitis	DISRC6IR	moderate	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[9]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[10]
Recessive X-linked ichthyosis	DISZY56W	moderate	Altered Expression	[11]
Fibrosarcoma	DISWX7MU	Disputed	Biomarker	[12]
Li-Fraumeni syndrome	DISR64XA	Disputed	Biomarker	[12]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[13]
Myocardial infarction	DIS655KI	Limited	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[14]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Protein CREG1 (CREG1) increases the response to substance of Arsenic.	[26]
Paclitaxel	DMLB81S	Approved	Protein CREG1 (CREG1) affects the response to substance of Paclitaxel.	[27]
Vinblastine	DM5TVS3	Approved	Protein CREG1 (CREG1) affects the response to substance of Vinblastine.	[27]

12 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 Protein CREG1 (CREG1).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein CREG1 (CREG1).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein CREG1 (CREG1).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein CREG1 (CREG1).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein CREG1 (CREG1).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein CREG1 (CREG1).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein CREG1 (CREG1).	[21]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Protein CREG1 (CREG1).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein CREG1 (CREG1).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein CREG1 (CREG1).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein CREG1 (CREG1).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Protein CREG1 (CREG1).	[25]

References

• [1] Transplantation of CREG modified embryonic stem cells improves cardiac function after myocardial infarction in mice.Biochem Biophys Res Commun. 2018 Sep 5;503(2):482-489. doi: 10.1016/j.bbrc.2018.04.160. Epub 2018 Jun 30.
• [2] Cellular Repressor of E1A-stimulated Genes, A New Potential Therapeutic Target for Atherosclerosis.Curr Drug Targets. 2017;18(15):1800-1804. doi: 10.2174/1389450117666161026111250.
• [3] Application of laser capture microdissection and differential display technique for screening of pathogenic genes involved in endometrial carcinoma.Int J Gynecol Cancer. 2007 Nov-Dec;17(6):1224-30. doi: 10.1111/j.1525-1438.2007.00947.x. Epub 2007 Apr 19.
• [4] CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance.PLoS One. 2017 May 1;12(5):e0176873. doi: 10.1371/journal.pone.0176873. eCollection 2017.
• [5] CREG1 stimulates brown adipocyte formation and ameliorates diet-induced obesity in mice.FASEB J. 2019 Jul;33(7):8069-8082. doi: 10.1096/fj.201802147RR. Epub 2019 Mar 27.
• [6] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [7] Cellular Repressor of E1A-Stimulated Genes Is a Critical Determinant of Vascular Remodeling in Response to Angiotensin II.Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):485-494. doi: 10.1161/ATVBAHA.116.308794. Epub 2017 Jan 5.
• [8] B7-CREG and ankylosing spondylitis.Br J Rheumatol. 1983 Nov;22(4 Suppl 2):129-33. doi: 10.1093/rheumatology/xxii.suppl_2.129.
• [9] Creg in Hepatocytes Ameliorates Liver Ischemia/Reperfusion Injury in a TAK1-Dependent Manner in Mice.Hepatology. 2019 Jan;69(1):294-313. doi: 10.1002/hep.30203.
• [10] Cellular repressor of E1A-stimulated gene overexpression in bone mesenchymal stem cells protects against rat myocardial infarction.Int J Cardiol. 2015 Mar 15;183:232-41. doi: 10.1016/j.ijcard.2015.01.059. Epub 2015 Jan 27.
• [11] Overexpression of CREG attenuates atherosclerotic endothelium apoptosis via VEGF/PI3K/AKT pathway.Atherosclerosis. 2011 Oct;218(2):543-51. doi: 10.1016/j.atherosclerosis.2011.08.002. Epub 2011 Aug 10.
• [12] CREG1 enhances p16(INK4a) -induced cellular senescence.Cell Cycle. 2011 Feb 1;10(3):518-30. doi: 10.4161/cc.10.3.14756. Epub 2011 Feb 1.
• [13] Lack of association between cellular repressor of E1A-stimulated genes (CREG) [corrected] polymorphisms and coronary artery disease in the Han population of North China.Clin Chim Acta. 2011 Jan 30;412(3-4):249-52. doi: 10.1016/j.cca.2010.10.008. Epub 2010 Oct 15.
• [14] A cellular repressor of E1A-stimulated genes that inhibits activation by E2F.Mol Cell Biol. 1998 Sep;18(9):5032-41. doi: 10.1128/MCB.18.9.5032.
• [15] HLA-DR versus HLA-B5-CREG antigens in rheumatoid arthritis (RA).Scand J Rheumatol. 1987;16(4):285-9. doi: 10.3109/03009748709102930.
• [16] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [17] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [18] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [19] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [20] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] Comparative mechanisms of PAH toxicity by benzo[a]pyrene and dibenzo[def,p]chrysene in primary human bronchial epithelial cells cultured at air-liquid interface. Toxicol Appl Pharmacol. 2019 Sep 15;379:114644.
• [23] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [26] Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility. Toxicol Appl Pharmacol. 2008 Jan 15;226(2):199-205. doi: 10.1016/j.taap.2007.09.004. Epub 2007 Sep 15.
• [27] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.