Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT43DI6J)

DOT Name Interferon regulatory factor 1 (IRF1)
Synonyms IRF-1
Gene Name IRF1
UniProt ID
IRF1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00605
Sequence
MPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAI
HTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLPPLTKNQR
KERKSKSSRDAKSKAKRKSCGDSSPDTFSDGLSSSTLPDDHSSYTVPGYMQDLEVEQALT
PALSPCAVSSTLPDWHIPVEVVPDSTSDLYNFQVSPMPSTSEATTDEDEEGKLPEDIMKL
LEQSEWQPTNVDGKGYLLNEPGVQPTSVYGDFSCKEEPEIDSPGGDIGLSLQRVFTDLKN
MDATWLDSLLTPVRLPSIQAIPCAP
Function
Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. Regulates transcription of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Competes with the transcriptional repressor ZBED2 for binding to a common consensus sequence in gene promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, RIGI, TNFSF10/TRAIL, ZBP1, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as GBP2, GBP5 and NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA; metabolic enzymes, such as ACOD1/IRG1. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.
KEGG Pathway
C-type lectin receptor sig.ling pathway (hsa04625 )
TNF sig.ling pathway (hsa04668 )
Prolactin sig.ling pathway (hsa04917 )
Pertussis (hsa05133 )
Human papillomavirus infection (hsa05165 )
Reactome Pathway
Interferon gamma signaling (R-HSA-877300 )
Interferon alpha/beta signaling (R-HSA-909733 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
Pyroptosis (R-HSA-5620971 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
31 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Interferon regulatory factor 1 (IRF1). [1]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Interferon regulatory factor 1 (IRF1). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Interferon regulatory factor 1 (IRF1). [3]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Interferon regulatory factor 1 (IRF1). [4]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Interferon regulatory factor 1 (IRF1). [5]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Interferon regulatory factor 1 (IRF1). [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Interferon regulatory factor 1 (IRF1). [8]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Interferon regulatory factor 1 (IRF1). [9]
Triclosan DMZUR4N Approved Triclosan increases the expression of Interferon regulatory factor 1 (IRF1). [10]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Interferon regulatory factor 1 (IRF1). [11]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Interferon regulatory factor 1 (IRF1). [12]
Marinol DM70IK5 Approved Marinol decreases the expression of Interferon regulatory factor 1 (IRF1). [13]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Interferon regulatory factor 1 (IRF1). [14]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Interferon regulatory factor 1 (IRF1). [15]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Interferon regulatory factor 1 (IRF1). [16]
Aspirin DM672AH Approved Aspirin increases the expression of Interferon regulatory factor 1 (IRF1). [17]
Menthol DMG2KW7 Approved Menthol decreases the expression of Interferon regulatory factor 1 (IRF1). [18]
Alitretinoin DMME8LH Approved Alitretinoin increases the expression of Interferon regulatory factor 1 (IRF1). [19]
Dacarbazine DMNPZL4 Approved Dacarbazine increases the expression of Interferon regulatory factor 1 (IRF1). [20]
Tamibarotene DM3G74J Phase 3 Tamibarotene increases the expression of Interferon regulatory factor 1 (IRF1). [3]
Fenretinide DMRD5SP Phase 3 Fenretinide increases the expression of Interferon regulatory factor 1 (IRF1). [21]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Interferon regulatory factor 1 (IRF1). [22]
DNCB DMDTVYC Phase 2 DNCB increases the expression of Interferon regulatory factor 1 (IRF1). [23]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Interferon regulatory factor 1 (IRF1). [24]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Interferon regulatory factor 1 (IRF1). [25]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Interferon regulatory factor 1 (IRF1). [26]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 increases the activity of Interferon regulatory factor 1 (IRF1). [27]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Interferon regulatory factor 1 (IRF1). [29]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Interferon regulatory factor 1 (IRF1). [15]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Interferon regulatory factor 1 (IRF1). [30]
geraniol DMS3CBD Investigative geraniol increases the expression of Interferon regulatory factor 1 (IRF1). [31]
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⏷ Show the Full List of 31 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Interferon regulatory factor 1 (IRF1). [6]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Interferon regulatory factor 1 (IRF1). [28]
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References

1 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
2 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.
3 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.
4 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
5 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.
6 Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
7 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.
8 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.
9 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
10 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
11 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
12 Decitabine up-regulates S100A2 expression and synergizes with IFN-gamma to kill uveal melanoma cells. Clin Cancer Res. 2007 Sep 1;13(17):5219-25. doi: 10.1158/1078-0432.CCR-07-0816.
13 Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
14 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.
15 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
16 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
17 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
18 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
19 Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
20 CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma. Eur J Clin Invest. 2007 Nov;37(11):887-96. doi: 10.1111/j.1365-2362.2007.01873.x.
21 The transforming growth factor-beta family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl)retinamide. Clin Cancer Res. 2005 Jun 15;11(12):4610-9.
22 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
23 Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker gene ID2, by contact sensitizers in human bulge-derived keratinocytes. J Biochem Mol Toxicol. 2010 Jan-Feb;24(1):10-20.
24 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
25 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
26 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.
27 Retinoic acid exerts dual regulatory actions on the expression and nuclear localization of interferon regulatory factor-1. Exp Biol Med (Maywood). 2006 May;231(5):619-31. doi: 10.1177/153537020623100517.
28 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
29 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
30 CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
31 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.