Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT11BATG)

• DOT Name: CCAAT/enhancer-binding protein zeta (CEBPZ)
• Synonyms: CCAAT-box-binding transcription factor; CBF; CCAAT-binding factor
• Gene Name: CEBPZ
• Related Disease:
  Cerebral infarction
  Acute myelomonocytic leukemia M4
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Bipolar disorder
  Brain neoplasm
  Central nervous system lymphoma
  Depression
  Encephalomalacia
  Glioma
  Herpes simplex encephalitis
  HIV infectious disease
  Intracranial meningioma
  Major depressive disorder
  Moyamoya disease
  Neoplasm
  Obstructive sleep apnea
  Scleroderma
  Stroke
  Systemic lupus erythematosus
  Systemic sclerosis
  Vascular disease
  High blood pressure
  Neuroblastoma
  Acute leukaemia
  Acute myelogenous leukaemia
  Chronic renal failure
  End-stage renal disease
  leukaemia
  Leukemia
  Sickle-cell anaemia
• UniProt ID: CEBPZ_HUMAN
• Pfam ID: PF03914
• Sequence:
  MAAVKEPLEFHAKRPWRPEEAVEDPDEEDEDNTSEAENGFSLEEVLRLGGTKQDYLMLAT
  LDENEEVIDGGKKGAIDDLQQGELEAFIQNLNLAKYTKASLVEEDEPAEKENSSKKEVKI
  PKINNKNTAESQRTSVNKVKNKNRPEPHSDENGSTTPKVKKDKQNIFEFFERQTLLLRPG
  GKWYDLEYSNEYSLKPQPQDVVSKYKTLAQKLYQHEINLFKSKTNSQKGASSTWMKAIVS
  SGTLGDRMAAMILLIQDDAVHTLQFVETLVNLVKKKGSKQQCLMALDTFKELLITDLLPD
  NRKLRIFSQRPFDKLEQLSSGNKDSRDRRLILWYFEHQLKHLVAEFVQVLETLSHDTLVT
  TKTRALTVAHELLCNKPEEEKALLVQVVNKLGDPQNRIATKASHLLETLLCKHPNMKGVV
  SGEVERLLFRSNISSKAQYYAICFLNQMALSHEESELANKLITVYFCFFRTCVKKKDVES
  KMLSALLTGVNRAYPYSQTGDDKVREQIDTLFKVLHIVNFNTSVQALMLLFQVMNSQQTI
  SDRYYTALYRKMLDPGLMTCSKQAMFLNLVYKSLKADIVLRRVKAFVKRLLQVTCQQMPP
  FICGALYLVSEILKAKPGLRSQLDDHPESDDEENFIDANDDEDMEKFTDADKETEIVKKL
  ETEETVPETDVETKKPEVASWVHFDNLKGGKQLNKYDPFSRNPLFCGAENTSLWELKKLS
  VHFHPSVALFAKTILQGNYIQYSGDPLQDFTLMRFLDRFVYRNPKPHKGKENTDSVVMQP
  KRKHFIKDIRHLPVNSKEFLAKEESQIPVDEVFFHRYYKKVAVKEKQKRDADEESIEDVD
  DEEFEELIDTFEDDNCFSSGKDDMDFAGNVKKRTKGAKDNTLDEDSEGSDDELGNLDDDE
  VSLGSMDDEEFAEVDEDGGTFMDVLDDESESVPELEVHSKVSTKKSKRKGTDDFDFAGSF
  QGPRKKKRNLNDSSLFVSAEEFGHLLDENMGSKFDNIGMNAMANKDNASLKQLRWEAERD
  DWLHNRDAKSIIKKKKHFKKKRIKTTQKTKKQRK
• Function: Stimulates transcription from the HSP70 promoter.

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral infarction	DISR1WNP	Definitive	Biomarker	[1]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[7]
Central nervous system lymphoma	DISBYQTA	Strong	Biomarker	[3]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Encephalomalacia	DISDJXKJ	Strong	Biomarker	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Herpes simplex encephalitis	DISGX28I	Strong	Biomarker	[11]
HIV infectious disease	DISO97HC	Strong	Biomarker	[12]
Intracranial meningioma	DISD09EF	Strong	Biomarker	[13]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[6]
Moyamoya disease	DISO62CA	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[16]
Scleroderma	DISVQ342	Strong	Biomarker	[17]
Stroke	DISX6UHX	Strong	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[19]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[17]
Vascular disease	DISVS67S	Strong	Biomarker	[20]
High blood pressure	DISY2OHH	moderate	Biomarker	[21]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[22]
Acute leukaemia	DISDQFDI	Limited	Genetic Variation	[23]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[24]
Chronic renal failure	DISGG7K6	Limited	Biomarker	[25]
End-stage renal disease	DISXA7GG	Limited	Biomarker	[25]
leukaemia	DISS7D1V	Limited	Biomarker	[24]
Leukemia	DISNAKFL	Limited	Biomarker	[24]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[26]

12 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 CCAAT/enhancer-binding protein zeta (CEBPZ).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[29]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[31]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[33]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[34]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[34]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[35]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CCAAT/enhancer-binding protein zeta (CEBPZ).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of CCAAT/enhancer-binding protein zeta (CEBPZ).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of CCAAT/enhancer-binding protein zeta (CEBPZ).	[37]

References

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• [2] Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias.J Clin Oncol. 2003 Dec 1;21(23):4413-22. doi: 10.1200/JCO.2003.03.166.
• [3] Clinical Value of Vascular Permeability Estimates Using Dynamic Susceptibility Contrast MRI: Improved Diagnostic Performance in Distinguishing Hypervascular Primary CNS Lymphoma from Glioblastoma.AJNR Am J Neuroradiol. 2018 Aug;39(8):1415-1422. doi: 10.3174/ajnr.A5732. Epub 2018 Jul 19.
• [4] Deletion of A-antigen in a human cancer cell line is associated with reduced promoter activity of CBF/NF-Y binding region, and possibly with enhanced DNA methylation of A transferase promoter.Glycoconj J. 1999 Oct;16(10):659-66. doi: 10.1023/a:1007085202379.
• [5] Regional Cerebral Blood Flow in the Posterior Cingulate and Precuneus and the Entorhinal Cortical Atrophy Score Differentiate Mild Cognitive Impairment and Dementia Due to Alzheimer Disease.AJNR Am J Neuroradiol. 2019 Oct;40(10):1658-1664. doi: 10.3174/ajnr.A6219. Epub 2019 Sep 12.
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• [13] Application of arterial spin labeling perfusion MRI to differentiate benign from malignant intracranial meningiomas.Eur J Radiol. 2017 Dec;97:31-36. doi: 10.1016/j.ejrad.2017.10.005. Epub 2017 Oct 7.
• [14] Bayesian Estimation of CBF Measured by DSC-MRI in Patients with Moyamoya Disease: Comparison with (15)O-Gas PET and Singular Value Decomposition.AJNR Am J Neuroradiol. 2019 Nov;40(11):1894-1900. doi: 10.3174/ajnr.A6248. Epub 2019 Oct 10.
• [15] Dynamic susceptibility contrast parametric imaging using accelerated dual-contrast echo planar imaging with keyhole.J Magn Reson Imaging. 2019 Aug;50(2):628-640. doi: 10.1002/jmri.26639. Epub 2019 Jan 8.
• [16] MRI evaluation of cerebrovascular reactivity in obstructive sleep apnea.J Cereb Blood Flow Metab. 2020 Jun;40(6):1328-1337. doi: 10.1177/0271678X19862182. Epub 2019 Jul 15.
• [17] B-Myb acts as a repressor of human COL1A1 collagen gene expression by interacting with Sp1 and CBF factors in scleroderma fibroblasts.Biochem J. 2004 Mar 1;378(Pt 2):609-16. doi: 10.1042/BJ20031110.
• [18] Altered gray matter volume, cerebral blood flow and functional connectivity in chronic stroke patients.Neurosci Lett. 2018 Jan 1;662:331-338. doi: 10.1016/j.neulet.2017.05.066. Epub 2017 Sep 15.
• [19] Alterations in Blood-Brain Barrier Permeability in Patients with Systemic Lupus Erythematosus.AJNR Am J Neuroradiol. 2019 Mar;40(3):470-477. doi: 10.3174/ajnr.A5990. Epub 2019 Feb 21.
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• [22] CCAAT-binding factor regulates expression of the beta1 subunit of soluble guanylyl cyclase gene in the BE2 human neuroblastoma cell line.Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11523-8. doi: 10.1073/pnas.1934338100. Epub 2003 Sep 22.
• [23] Leukemogenic potency of the novel FLT3-N676K mutant.Ann Hematol. 2016 Apr;95(5):783-91. doi: 10.1007/s00277-016-2616-z. Epub 2016 Feb 19.
• [24] A tool compound targeting the core binding factor Runt domain to disrupt binding to CBF in leukemic cells.Leuk Lymphoma. 2018 Sep;59(9):2188-2200. doi: 10.1080/10428194.2017.1410882. Epub 2017 Dec 18.
• [25] Decreased cerebral blood flow and improved cognitive function in patients with end-stage renal disease after peritoneal dialysis: An arterial spin-labelling study.Eur Radiol. 2019 Mar;29(3):1415-1424. doi: 10.1007/s00330-018-5675-9. Epub 2018 Aug 13.
• [26] Cerebral Blood Flow and Marrow Diffusion Alterations in Children with Sickle Cell Anemia after Bone Marrow Transplantation and Transfusion.AJNR Am J Neuroradiol. 2018 Nov;39(11):2132-2139. doi: 10.3174/ajnr.A5830. Epub 2018 Oct 11.
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• [30] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [31] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [32] 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.
• [33] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [34] Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
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• [37] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [38] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.