Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYOR3PV)

• DOT Name: Nucleolar complex protein 3 homolog (NOC3L)
• Synonyms: NOC3 protein homolog; Factor for adipocyte differentiation 24; NOC3-like protein; Nucleolar complex-associated protein 3-like protein
• Gene Name: NOC3L
• Related Disease:
  Alzheimer disease
  Colorectal carcinoma
  Esophageal cancer
  Gastric cancer
  Stomach cancer
• UniProt ID: NOC3L_HUMAN
• PDB ID: 8FKV; 8FKW; 8FKX; 8FKY
• Pfam ID: PF03914 ; PF07540
• Sequence:
  MKARRNKKQIPSFRKLIKTSKVKLENKLKNKQFKQQSTLKKYRKEQRKLRQAVKDAVSKK
  PIPLENPKEKRPGKRIEREEEEEEEALPLDMMDEDDLQLMKDLGQRVSFLTRDLSSSEPV
  HAKKRKHERIIDKYEKIPRTLQTAPEKELIHLLPIKDKSGIIPQTREKPVTDSNKDEEDQ
  EEERELEEEIIEDPIQELTIEEHLIERKKKLQEKKMHIAALASAILSDPENNIKKLKELR
  SMLMEQDPDVAVTVRKLVIVSLMELFKDITPSYKIRPLTEAEKSTKTRKETQKLREFEEG
  LVSQYKFYLENLEQMVKDWKQRKLKKSNVVSLKAYKGLAEVAVKSLCELLVALPHFNFHN
  NIIVLIVPLMNDMSKLISEMCCEAVKKLFKQDKLGQASLGVIKVISGFVKGRNYEVRPEM
  LKTFLCLRIKEVEVKKDTEDINKPKKFMTFKEKRKSLSRMQRKWKKAEEKLERELREAEA
  SESTEKKLKLHTETLNIVFVTYFRILKKAQRSPLLPAVLEGLAKFAHLINVEFFDDLLVV
  LHTLIESGDLSYQESLHCVQTAFHILSGQGDVLNIDPLKFYTHLYKTLFKLHAGATNEGV
  EIVLQCLDVMLTKRRKQVSQQRALAFIKRLCTLALHVLPNSSIGILATTRILMHTFPKTD
  LLLDSESQGSGVFLPELDEPEYCNAQNTALWELHALRRHYHPIVQRFAAHLIAGAPSEGS
  GALKPELSRRSATELFEAYSMAEMTFNPPVESSNPKIKGKFLQGDSFLNEDLNQLIKRYS
  SEVATESPLDFTKYLKTSLH
• Function: May be required for adipogenesis.
• Tissue Specificity: Expressed in colon, heart, kidney, liver, lung, placenta, skeletal muscle, small intestine, spleen and thymus.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[3]
Gastric cancer	DISXGOUK	moderate	Genetic Variation	[4]
Stomach cancer	DISKIJSX	moderate	Genetic Variation	[4]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Nucleolar complex protein 3 homolog (NOC3L) affects the response to substance of Topotecan.	[22]
Afimoxifene	DMFORDT	Phase 2	Nucleolar complex protein 3 homolog (NOC3L) affects the response to substance of Afimoxifene.	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Nucleolar complex protein 3 homolog (NOC3L).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nucleolar complex protein 3 homolog (NOC3L).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Nucleolar complex protein 3 homolog (NOC3L).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nucleolar complex protein 3 homolog (NOC3L).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nucleolar complex protein 3 homolog (NOC3L).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[11]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[19]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[20]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Nucleolar complex protein 3 homolog (NOC3L).	[21]

References

• [1] Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study.Lancet Neurol. 2011 Sep;10(9):785-96. doi: 10.1016/S1474-4422(11)70156-9. Epub 2011 Jul 27.
• [2] Genetic association of PLCE1, C11orf92-C11orf93, and NOC3L with colorectal cancer risk in the Han population.Tumour Biol. 2014 Mar;35(3):1813-7. doi: 10.1007/s13277-013-1242-9. Epub 2013 Oct 22.
• [3] Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations.Nat Genet. 2011 Jun 5;43(7):679-84. doi: 10.1038/ng.849.
• [4] Probabilistic natural mapping of gene-level tests for genome-wide association studies.Brief Bioinform. 2018 Jul 20;19(4):545-553. doi: 10.1093/bib/bbx002.
• [5] 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.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] 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.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [14] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] 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.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] 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.
• [21] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [23] Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2730-5. doi: 10.1073/pnas.1018872108. Epub 2011 Apr 11.