Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNT7R33)

• DOT Name: Nucleolar complex protein 2 homolog (NOC2L)
• Synonyms: Protein NOC2 homolog; NOC2-like protein; Novel INHAT repressor
• Gene Name: NOC2L
• Related Disease:
  Hepatocellular carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Achromatopsia
  Adenoma
  Advanced cancer
  Alzheimer disease
  Autism spectrum disorder
  Bone osteosarcoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Epithelial neoplasm
  Esophageal adenocarcinoma
  Familial multiple trichoepithelioma
  Glioma
  Metastatic malignant neoplasm
  Neoplasm
  Neuralgia
  Oral cavity squamous cell carcinoma
  Osteosarcoma
  Persistent truncus arteriosus
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Psoriatic arthritis
  Retinitis pigmentosa
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Stomach cancer
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Glioblastoma multiforme
  Amyotrophic lateral sclerosis
  Atrial fibrillation
  Choroideremia
  Pancreatic cancer
  Squamous cell carcinoma
  Type-1 diabetes
  Vitelliform macular dystrophy
• UniProt ID: NOC2L_HUMAN
• PDB ID: 8FKV; 8FKW; 8FKX; 8FKY
• Pfam ID: PF03715
• Sequence:
  MAAAGSRKRRLAELTVDEFLASGFDSESESESENSPQAETREAREAARSPDKPGGSPSAS
  RRKGRASEHKDQLSRLKDRDPEFYKFLQENDQSLLNFSDSDSSEEEEGPFHSLPDVLEEA
  SEEEDGAEEGEDGDRVPRGLKGKKNSVPVTVAMVERWKQAAKQRLTPKLFHEVVQAFRAA
  VATTRGDQESAEANKFQVTDSAAFNALVTFCIRDLIGCLQKLLFGKVAKDSSRMLQPSSS
  PLWGKLRVDIKAYLGSAIQLVSCLSETTVLAAVLRHISVLVPCFLTFPKQCRMLLKRMVI
  VWSTGEESLRVLAFLVLSRVCRHKKDTFLGPVLKQMYITYVRNCKFTSPGALPFISFMQW
  TLTELLALEPGVAYQHAFLYIRQLAIHLRNAMTTRKKETYQSVYNWQYVHCLFLWCRVLS
  TAGPSEALQPLVYPLAQVIIGCIKLIPTARFYPLRMHCIRALTLLSGSSGAFIPVLPFIL
  EMFQQVDFNRKPGRMSSKPINFSVILKLSNVNLQEKAYRDGLVEQLYDLTLEYLHSQAHC
  IGFPELVLPVVLQLKSFLRECKVANYCRQVQQLLGKVQENSAYICSRRQRVSFGVSEQQA
  VEAWEKLTREEGTPLTLYYSHWRKLRDREIQLEISGKERLEDLNFPEIKRRKMADRKDED
  RKQFKDLFDLNSSEEDDTEGFSERGILRPLSTRHGVEDDEEDEEEGEEDSSNSEDGDPDA
  EAGLAPGELQQLAQGPEDELEDLQLSEDD
• Function: Acts as an inhibitor of histone acetyltransferase activity; prevents acetylation of all core histones by the EP300/p300 histone acetyltransferase at p53/TP53-regulated target promoters in a histone deacetylases (HDAC)-independent manner. Acts as a transcription corepressor of p53/TP53- and TP63-mediated transactivation of the p21/CDKN1A promoter. Involved in the regulation of p53/TP53-dependent apoptosis. Associates together with TP63 isoform TA*-gamma to the p21/CDKN1A promoter.
• Reactome Pathway: Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Thyroid cancer	DIS3VLDH	Definitive	Biomarker	[2]
Thyroid gland carcinoma	DISMNGZ0	Definitive	Biomarker	[2]
Thyroid tumor	DISLVKMD	Definitive	Biomarker	[2]
Achromatopsia	DISKL51I	Strong	Biomarker	[3]
Adenoma	DIS78ZEV	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[11]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[12]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Neuralgia	DISWO58J	Strong	Biomarker	[17]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Biomarker	[18]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Persistent truncus arteriosus	DISRZ8EA	Strong	Biomarker	[19]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[22]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[23]
Bladder cancer	DISUHNM0	moderate	Genetic Variation	[24]
Breast cancer	DIS7DPX1	moderate	Biomarker	[25]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[25]
Stomach cancer	DISKIJSX	moderate	Biomarker	[26]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[27]
Urinary bladder cancer	DISDV4T7	moderate	Genetic Variation	[24]
Urinary bladder neoplasm	DIS7HACE	moderate	Genetic Variation	[24]
Glioblastoma multiforme	DISK8246	Disputed	Biomarker	[28]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[29]
Atrial fibrillation	DIS15W6U	Limited	Biomarker	[30]
Choroideremia	DISH4N9B	Limited	Biomarker	[31]
Pancreatic cancer	DISJC981	Limited	Biomarker	[32]
Squamous cell carcinoma	DISQVIFL	Limited	Genetic Variation	[33]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[34]
Vitelliform macular dystrophy	DISEFYYN	Limited	Biomarker	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Nucleolar complex protein 2 homolog (NOC2L).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Nucleolar complex protein 2 homolog (NOC2L).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nucleolar complex protein 2 homolog (NOC2L).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Nucleolar complex protein 2 homolog (NOC2L).	[46]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Nucleolar complex protein 2 homolog (NOC2L).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[40]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[42]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[43]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[44]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Nucleolar complex protein 2 homolog (NOC2L).	[44]

References

• [1] Development of a Novel Histone Deacetylase-Targeted Near-Infrared Probe for Hepatocellular Carcinoma Imaging and Fluorescence Image-Guided Surgery.Mol Imaging Biol. 2020 Jun;22(3):476-485. doi: 10.1007/s11307-019-01389-4.
• [2] Novel design of NIR-triggered plasmonic nanodots capped mesoporous silica nanoparticles loaded with natural capsaicin to inhibition of metastasis of human papillary thyroid carcinoma B-CPAP cells in thyroid cancer chemo-photothermal therapy.J Photochem Photobiol B. 2019 Aug;197:111534. doi: 10.1016/j.jphotobiol.2019.111534. Epub 2019 Jun 15.
• [3] Multimodal imaging including semiquantitative short-wavelength and near-infrared autofluorescence in achromatopsia.Sci Rep. 2018 Apr 4;8(1):5665. doi: 10.1038/s41598-018-23919-w.
• [4] Potential Red-Flag Identification of Colorectal Adenomas with Wide-Field Fluorescence Molecular Endoscopy.Theranostics. 2018 Feb 5;8(6):1458-1467. doi: 10.7150/thno.22033. eCollection 2018.
• [5] Cancer neovasculature-targeted near-infrared photoimmunotherapy (NIR-PIT) for gastric cancer: different mechanisms of phototoxicity compared to cell membrane-targeted NIR-PIT.Gastric Cancer. 2020 Jan;23(1):82-94. doi: 10.1007/s10120-019-00988-y. Epub 2019 Jul 13.
• [6] NIR fluorescent probes with good water-solubility for detection of amyloid beta aggregates in Alzheimer's disease.J Mater Chem B. 2019 Sep 18;7(36):5535-5540. doi: 10.1039/c9tb01012b.
• [7] Replication of a rare risk haplotype on 1p36.33 for autism spectrum disorder.Hum Genet. 2018 Oct;137(10):807-815. doi: 10.1007/s00439-018-1939-3. Epub 2018 Oct 1.
• [8] Noninvasive Multimodal Imaging of Osteosarcoma and Lymph Nodes Using a (99m)Tc-Labeled Biomineralization Nanoprobe.Anal Chem. 2018 Apr 3;90(7):4529-4534. doi: 10.1021/acs.analchem.7b04925. Epub 2018 Mar 13.
• [9] Thermo- and pH-dual responsive polymeric micelles with upper critical solution temperature behavior for photoacoustic imaging-guided synergistic chemo-photothermal therapy against subcutaneous and metastatic breast tumors.Theranostics. 2018 Jul 16;8(15):4097-4115. doi: 10.7150/thno.26195. eCollection 2018.
• [10] Therapeutic effect of the treatment for colorectal cancer with adenoviral vectors mediated estrogen receptor gene therapy combined with thermotherapy.J Cancer Res Clin Oncol. 2014 Apr;140(4):623-32. doi: 10.1007/s00432-014-1611-9. Epub 2014 Feb 15.
• [11] In vivo and in vitro application of near-infrared fiber optic probe for Ehrlich carcinoma distinction: Towards the development of real-time tumor margins assessment tool.Spectrochim Acta A Mol Biomol Spectrosc. 2019 Apr 15;213:12-18. doi: 10.1016/j.saa.2019.01.061. Epub 2019 Jan 16.
• [12] NIR absorbing reduced graphene oxide for photothermal radiotherapy for treatment of esophageal cancer.J Photochem Photobiol B. 2019 May;194:188-193. doi: 10.1016/j.jphotobiol.2019.03.014. Epub 2019 Mar 22.
• [13] Tyrosine kinase inhibitor induced growth factor receptor upregulation enhances the efficacy of near-infrared targeted photodynamic therapy in esophageal adenocarcinoma cell lines.Oncotarget. 2017 May 2;8(18):29846-29856. doi: 10.18632/oncotarget.16165.
• [14] Phototheranostics: Active Targeting of Orthotopic Glioma Using Biomimetic Proteolipid Nanoparticles.ACS Nano. 2019 Jan 22;13(1):386-398. doi: 10.1021/acsnano.8b06556. Epub 2018 Dec 27.
• [15] Highly bright and stable NIR-BRET with blue-shifted coelenterazine derivatives for deep-tissue imaging of molecular events in vivo.Theranostics. 2019 Apr 13;9(9):2646-2661. doi: 10.7150/thno.32219. eCollection 2019.
• [16] Modulation of tumor microenvironment using a TLR-7/8 agonist-loaded nanoparticle system that exerts low-temperature hyperthermia and immunotherapy for in situ cancer vaccination.Biomaterials. 2020 Feb;230:119629. doi: 10.1016/j.biomaterials.2019.119629. Epub 2019 Nov 15.
• [17] Effect of NIR laser therapy by MLS-MiS source against neuropathic pain in rats: in vivo and ex vivo analysis.Sci Rep. 2019 Jun 26;9(1):9297. doi: 10.1038/s41598-019-45469-5.
• [18] Syngeneic Mouse Models of Oral Cancer Are Effectively Targeted by Anti-CD44-Based NIR-PIT.Mol Cancer Res. 2017 Dec;15(12):1667-1677. doi: 10.1158/1541-7786.MCR-17-0333. Epub 2017 Sep 18.
• [19] Nanoscale Covalent Organic Framework for Combinatorial Antitumor Photodynamic and Photothermal Therapy.ACS Nano. 2019 Nov 26;13(11):13304-13316. doi: 10.1021/acsnano.9b06467. Epub 2019 Nov 8.
• [20] Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study.Res Microbiol. 2019 Jan-Feb;170(1):43-52. doi: 10.1016/j.resmic.2018.09.002. Epub 2018 Oct 4.
• [21] An ALP-activatable and mitochondria-targeted probe for prostate cancer-specific bimodal imaging and aggregation-enhanced photothermal therapy.Nanoscale. 2019 Mar 28;11(13):6307-6314. doi: 10.1039/c9nr00913b.
• [22] Hypoxia-triggered single molecule probe for high-contrast NIR II/PA tumor imaging and robust photothermal therapy.Theranostics. 2018 Nov 15;8(21):6025-6034. doi: 10.7150/thno.26607. eCollection 2018.
• [23] Quantitative Comparison of Near-infrared Versus Short-wave Autofluorescence Imaging in Monitoring Progression of Retinitis Pigmentosa.Am J Ophthalmol. 2018 Oct;194:120-125. doi: 10.1016/j.ajo.2018.07.012. Epub 2018 Jul 24.
• [24] A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging.Nat Commun. 2019 Oct 24;10(1):4861. doi: 10.1038/s41467-019-12848-5.
• [25] Folic acid-functionalized graphene oxide nanosheets via plasma etching as a platform to combine NIR anticancer phototherapy and targeted drug delivery.Mater Sci Eng C Mater Biol Appl. 2020 Feb;107:110201. doi: 10.1016/j.msec.2019.110201. Epub 2019 Sep 13.
• [26] Enhanced legumain-recognition and NIR controlled released of cisplatin-indocyanine nanosphere against gastric carcinoma.Eur J Pharmacol. 2017 Jan 5;794:184-192. doi: 10.1016/j.ejphar.2016.11.039. Epub 2016 Nov 25.
• [27] A uPAR targeted nanoplatform with an NIR laser-responsive drug release property for tri-modal imaging and synergistic photothermal-chemotherapy of triple-negative breast cancer.Biomater Sci. 2020 Jan 21;8(2):720-738. doi: 10.1039/c9bm01495k.
• [28] Scaffolds biomimicking macrophages for a glioblastoma NIR-Ib imaging guided photothermal therapeutic strategy by crossing Blood-Brain Barrier.Biomaterials. 2019 Aug;211:48-56. doi: 10.1016/j.biomaterials.2019.04.026. Epub 2019 May 6.
• [29] Proteomic analysis of exosome-enriched fractions derived from cerebrospinal fluid of amyotrophic lateral sclerosis patients.Neurosci Res. 2020 Nov;160:43-49. doi: 10.1016/j.neures.2019.10.010. Epub 2019 Oct 24.
• [30] Patterns and Intensities of Near-Infrared and Short-Wavelength Fundus Autofluorescence in Choroideremia Probands and Carriers.Invest Ophthalmol Vis Sci. 2019 Sep 3;60(12):3752-3761. doi: 10.1167/iovs.19-27366.
• [31] Near-infrared autofluorescence in young choroideremia patients.Ophthalmic Genet. 2019 Oct;40(5):421-427. doi: 10.1080/13816810.2019.1666881. Epub 2019 Sep 21.
• [32] Polydopamine-tailored paclitaxel-loaded polymeric microspheres with adhered NIR-controllable gold nanoparticles for chemo-phototherapy of pancreatic cancer.Drug Deliv. 2019 Dec;26(1):629-640. doi: 10.1080/10717544.2019.1628118.
• [33] An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas.Oncotarget. 2018 Feb 5;9(17):13517-13529. doi: 10.18632/oncotarget.24399. eCollection 2018 Mar 2.
• [34] Clinical and Genetic Characteristics of Non-Insulin-Requiring Glutamic Acid Decarboxylase (GAD) Autoantibody-Positive Diabetes: A Nationwide Survey in Japan.PLoS One. 2016 May 13;11(5):e0155643. doi: 10.1371/journal.pone.0155643. eCollection 2016.
• [35] Multimodal Imaging in Best Vitelliform Macular Dystrophy.Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2012-2022. doi: 10.1167/iovs.19-26571.
• [36] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [37] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [38] 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.
• [39] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [40] 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.
• [41] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [42] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [43] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [44] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [45] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [46] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.