Details of Drug Off-Target (DOT)

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

• DOT Name: Inhibitor of growth protein 1 (ING1)
• Gene Name: ING1
• Related Disease:
  Osteosarcoma
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Bladder cancer
  Bone osteosarcoma
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma
  Chronic granulomatous disease
  Colon cancer
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Gastric neoplasm
  Glioblastoma multiforme
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Hutchinson-Gilford progeria syndrome
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Epithelial ovarian cancer
  Metastatic malignant neoplasm
  Ovarian neoplasm
  Squamous cell carcinoma
  Asthma
  Contact dermatitis
  Gastric cancer
  Hypopharyngeal squamous cell carcinoma
  Laryngeal squamous cell carcinoma
  Malaria
  Melanoma
  Neuroblastoma
  Non-small-cell lung cancer
  Oral cavity squamous cell carcinoma
  Oropharyngeal squamous cell carcinoma
  Plasma cell myeloma
  Type-1/2 diabetes
  Head-neck squamous cell carcinoma
• UniProt ID: ING1_HUMAN
• PDB ID: 2QIC
• Pfam ID: PF12998
• Sequence:
  MSFVECPYHSPAERLVAEADEGGPSAITGMGLCFRCLLFSFSGRSGVEGGRVDLNVFGSL
  GLQPWIGSSRCWGGPCSSALRCGWFSSWPPPSKSAIPIGGGSRGAGRVSRWPPPHWLEAW
  RVSPLPLSPLSPATFGRGFIAVAVIPGLWARGRGCSSDRLPRPAGPARRQFQAASLLTRG
  WGRAWPWKQILKELDECYERFSRETDGAQKRRMLHCVQRALIRSQELGDEKIQIVSQMVE
  LVENRTRQVDSHVELFEAQQELGDTAGNSGKAGADRPKGEAAAQADKPNSKRSRRQRNNE
  NRENASSNHDHDDGASGTPKEKKAKTSKKKKRSKAKAEREASPADLPIDPNEPTYCLCNQ
  VSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGENEKTMDKALEKSKKERAY
  NR
• Function: Cooperates with p53/TP53 in the negative regulatory pathway of cell growth by modulating p53-dependent transcriptional activation. Implicated as a tumor suppressor gene.
• Tissue Specificity: Isoform 2 was expressed in all normal tissues and cells examined, as well as in all breast cancer and melanoma cell lines examined. Isoform 3 was expressed in testis, liver, and kidney, weakly expressed in colon and brain and not expressed in breast and cultured melanocytes. Isoform 4 was highly expressed in testis and weakly expressed in brain, but not expressed in breast, colon, kidney, melanocytes, breast cancer or melanoma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Chronic granulomatous disease	DIS9ZR24	Strong	Genetic Variation	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[13]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[16]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[16]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[14]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Genetic Variation	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[18]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[19]
Prostate cancer	DISF190Y	Strong	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[20]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	moderate	Altered Expression	[19]
Metastatic malignant neoplasm	DIS86UK6	moderate	Genetic Variation	[21]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[19]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[22]
Asthma	DISW9QNS	Limited	Altered Expression	[23]
Contact dermatitis	DISQ3AU0	Limited	Biomarker	[24]
Gastric cancer	DISXGOUK	Limited	Biomarker	[14]
Hypopharyngeal squamous cell carcinoma	DISDDD65	Limited	SomaticCausalMutation	[25]
Laryngeal squamous cell carcinoma	DIS9UUVF	Limited	SomaticCausalMutation	[25]
Malaria	DISQ9Y50	Limited	Biomarker	[26]
Melanoma	DIS1RRCY	Limited	Altered Expression	[27]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[28]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[29]
Oral cavity squamous cell carcinoma	DISQVJVA	Limited	SomaticCausalMutation	[25]
Oropharyngeal squamous cell carcinoma	DIS7D7QV	Limited	SomaticCausalMutation	[25]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[15]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[30]
Head-neck squamous cell carcinoma	DISF7P24	No Known	Unknown	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Inhibitor of growth protein 1 (ING1).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Inhibitor of growth protein 1 (ING1).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Inhibitor of growth protein 1 (ING1).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Inhibitor of growth protein 1 (ING1).	[35]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Inhibitor of growth protein 1 (ING1).	[36]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Inhibitor of growth protein 1 (ING1).	[37]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Inhibitor of growth protein 1 (ING1).	[38]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Inhibitor of growth protein 1 (ING1).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Inhibitor of growth protein 1 (ING1).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Inhibitor of growth protein 1 (ING1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Inhibitor of growth protein 1 (ING1).	[42]

References

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• [2] ING1 and p53 tumor suppressor gene alterations in adenocarcinomas of the esophagogastric junction.Cancer Lett. 2003 Mar 20;192(1):109-16. doi: 10.1016/s0304-3835(02)00635-3.
• [3] Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma.Cell Death Dis. 2018 Oct 9;9(10):1032. doi: 10.1038/s41419-018-1058-z.
• [4] Loss of heterozygosity of chromosome 13q33-34 region and molecular analysis of ING1 and p53 genes in bladder carcinoma.Mol Biol Rep. 2015 Feb;42(2):507-16. doi: 10.1007/s11033-014-3794-1. Epub 2014 Oct 17.
• [5] Effects of the Pentapeptide P33 on Memory and Synaptic Plasticity in APP/PS1 Transgenic Mice: A Novel Mechanism Presenting the Protein Fe65 as a Target.Int J Mol Sci. 2019 Jun 22;20(12):3050. doi: 10.3390/ijms20123050.
• [6] The tumor suppressor p33ING1b enhances taxol-induced apoptosis by p53-dependent pathway in human osteosarcoma U2OS cells.Cancer Biol Ther. 2005 Jan;4(1):39-47. doi: 10.4161/cbt.4.1.1372. Epub 2005 Jan 15.
• [7] No ING1 mutations in human brain tumours but reduced expression in high malignancy grades of astrocytoma.Int J Cancer. 2004 Apr 10;109(3):476-9. doi: 10.1002/ijc.11715.
• [8] Stromal ING1 expression induces a secretory phenotype and correlates with breast cancer patient survival.Mol Cancer. 2015 Aug 27;14:164. doi: 10.1186/s12943-015-0434-x.
• [9] Genetic alterations of tumor suppressor ING1 in human non-small cell lung cancer.Oncol Rep. 2011 Apr;25(4):1073-81. doi: 10.3892/or.2011.1172. Epub 2011 Jan 31.
• [10] Aberrant [correction of Abberant] cytosolic calcium ion mobilization in chronic granulomatous disease neutrophils.Inflammation. 2004 Jun;28(3):133-8. doi: 10.1023/b:ifla.0000039559.96659.d9.
• [11] Cloning of a novel gene (ING1L) homologous to ING1, a candidate tumor suppressor.Cytogenet Cell Genet. 1998;83(3-4):232-5. doi: 10.1159/000015188.
• [12] Genetic alterations and expression of inhibitor of growth 1 in human sporadic colorectal cancer.World J Gastroenterol. 2005 Oct 21;11(39):6120-4. doi: 10.3748/wjg.v11.i39.6120.
• [13] Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.Cancer Res. 2001 Jun 1;61(11):4345-9.
• [14] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [15] The inhibitor of growth 1 (ING1) proteins suppress angiogenesis and differentially regulate angiopoietin expression in glioblastoma cells.Oncol Res. 2009;18(2-3):95-105. doi: 10.3727/096504009789954645.
• [16] Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas.Gene. 2005 Aug 15;356:109-17. doi: 10.1016/j.gene.2005.02.014.
• [17] The emerging role of alternative splicing in senescence and aging.Aging Cell. 2017 Oct;16(5):918-933. doi: 10.1111/acel.12646. Epub 2017 Jul 13.
• [18] Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human lung cancer.Oncol Rep. 2006 Mar;15(3):545-9.
• [19] Epigenetic and genetic alterations of p33ING1b in ovarian cancer.Carcinogenesis. 2005 Apr;26(4):855-63. doi: 10.1093/carcin/bgi011. Epub 2005 Jan 27.
• [20] The tumor suppressor ING1b is a novel corepressor for the androgen receptor and induces cellular senescence in prostate cancer cells.J Mol Cell Biol. 2016 Jun;8(3):207-20. doi: 10.1093/jmcb/mjw007. Epub 2016 Mar 18.
• [21] MicroRNA let-7b suppresses human gastric cancer malignancy by targeting ING1.Cancer Gene Ther. 2015 Apr;22(3):122-9. doi: 10.1038/cgt.2014.75. Epub 2015 Jan 23.
• [22] Nuclear entrapment of p33ING1b by inhibition of exportin-1: A trigger of apoptosis in head and neck squamous cell cancer.Cell Mol Biol (Noisy-le-grand). 2018 Apr 30;64(5):66-72.
• [23] CaMKII is essential for the proasthmatic effects of oxidation.Sci Transl Med. 2013 Jul 24;5(195):195ra97. doi: 10.1126/scitranslmed.3006135.
• [24] Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin modelDevelopment of the SENS-IS assay. Toxicol In Vitro. 2015 Jun;29(4):787-802.
• [25] Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas.Cancer Res. 2000 Jun 15;60(12):3143-6.
• [26] Plasmodium P47: a key gene for malaria transmission by mosquito vectors.Curr Opin Microbiol. 2017 Dec;40:168-174. doi: 10.1016/j.mib.2017.11.029. Epub 2017 Dec 8.
• [27] Phosphorylation of the tumor suppressor p33(ING1b) at Ser-126 influences its protein stability and proliferation of melanoma cells.FASEB J. 2007 Nov;21(13):3705-16. doi: 10.1096/fj.07-8069com. Epub 2007 Jun 21.
• [28] Decreased expression of the candidate tumor suppressor gene ING1 is associated with poor prognosis in advanced neuroblastomas.Oncol Rep. 2004 Oct;12(4):811-6.
• [29] Down-regulation of miR-500 and miR-628 suppress non-small cell lung cancer proliferation, migration and invasion by targeting ING1.Biomed Pharmacother. 2018 Dec;108:1628-1639. doi: 10.1016/j.biopha.2018.09.145. Epub 2018 Oct 10.
• [30] Euterpe oleracea Mart. seed extract protects against renal injury in diabetic and spontaneously hypertensive rats: role of inflammation and oxidative stress.Eur J Nutr. 2018 Mar;57(2):817-832. doi: 10.1007/s00394-016-1371-1. Epub 2017 Jan 20.
• [31] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [32] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [33] 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.
• [34] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [35] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [36] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [37] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [38] 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.
• [39] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [40] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [41] 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.
• [42] 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.