Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXSE7KW)

• DOT Name: Nuclear transcription factor Y subunit beta (NFYB)
• Synonyms: CAAT box DNA-binding protein subunit B; Nuclear transcription factor Y subunit B; NF-YB
• Gene Name: NFYB
• Related Disease:
  Acute myelogenous leukaemia
  Acute myocardial infarction
  Agranulocytosis
  Colorectal carcinoma
  Essential hypertension
  Lung cancer
  Lung carcinoma
  Non-insulin dependent diabetes
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Neuroblastoma
• UniProt ID: NFYB_HUMAN
• PDB ID: 1N1J; 4AWL; 4CSR; 6QMP; 6QMQ; 6QMS; 7AH8
• Pfam ID: PF00808
• Sequence:
  MTMDGDSSTTDASQLGISADYIGGSHYVIQPHDDTEDSMNDHEDTNGSKESFREQDIYLP
  IANVARIMKNAIPQTGKIAKDAKECVQECVSEFISFITSEASERCHQEKRKTINGEDILF
  AMSTLGFDSYVEPLKLYLQKFREAMKGEKGIGGAVTATDGLSEELTEEAFTNQLPAGLIT
  TDGQQQNVMVYTTSYQQISGVQQIQFS
• Function: Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  Tuberculosis (hsa05152)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)
  ATF6 (ATF6-alpha) activates chaperone genes (R-HSA-381183)
  FOXO-mediated transcription of cell death genes (R-HSA-9614657)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[2]
Agranulocytosis	DISJS4LS	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[7]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[8]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[9]

17 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 Nuclear transcription factor Y subunit beta (NFYB).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Nuclear transcription factor Y subunit beta (NFYB).	[15]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[16]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[20]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[21]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[22]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[23]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Nuclear transcription factor Y subunit beta (NFYB).	[24]

References

• [1] Transcriptional repression of Cdc25B by IER5 inhibits the proliferation of leukemic progenitor cells through NF-YB and p300 in acute myeloid leukemia.PLoS One. 2011;6(11):e28011. doi: 10.1371/journal.pone.0028011. Epub 2011 Nov 23.
• [2] A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction.Basic Res Cardiol. 2018 Aug 10;113(5):38. doi: 10.1007/s00395-018-0697-7.
• [3] Novel Association between Flavin-Containing Monooxygenase 3 Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population.Ann Nutr Metab. 2019;74(3):200-206. doi: 10.1159/000497314. Epub 2019 Feb 27.
• [4] NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in colorectal cancer via the enhancement of CHK1 signaling.Cancer Lett. 2018 Feb 28;415:58-72. doi: 10.1016/j.canlet.2017.11.040. Epub 2017 Dec 22.
• [5] Association of polymorphisms in prolylcarboxypeptidase and chymase genes with essential hypertension in the Chinese Han population.J Renin Angiotensin Aldosterone Syst. 2013 Sep;14(3):263-70. doi: 10.1177/1470320312448949. Epub 2012 Jun 7.
• [6] Haplotype-tagging single nucleotide polymorphisms in the GSTP1 gene promoter and susceptibility to lung cancer.Cancer Detect Prev. 2009;32(5-6):403-15. doi: 10.1016/j.cdp.2009.02.004. Epub 2009 Mar 17.
• [7] Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus.J Diabetes Res. 2019 May 7;2019:4902301. doi: 10.1155/2019/4902301. eCollection 2019.
• [8] Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma.Biomed Res Int. 2019 Apr 28;2019:9734576. doi: 10.1155/2019/9734576. eCollection 2019.
• [9] Drd2 expression in the high alcohol-preferring and low alcohol-preferring mice.Mamm Genome. 2008 Feb;19(2):69-76. doi: 10.1007/s00335-007-9089-2. Epub 2008 Jan 23.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] 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.
• [13] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [17] Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] 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.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [22] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.
• [23] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [24] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.