Details of Drug Off-Target (DOT)

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

• DOT Name: Protein NDRG3 (NDRG3)
• Synonyms: N-myc downstream-regulated gene 3 protein
• Gene Name: NDRG3
• Related Disease:
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Cerebral infarction
  Gastric cancer
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Colorectal carcinoma
• UniProt ID: NDRG3_HUMAN
• PDB ID: 6L4B; 6L4G; 6L4H
• Pfam ID: PF03096
• Sequence:
  MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGVVHVTIRGLPKGNRPVILTY
  HDIGLNHKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEML
  PPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSG
  LTTNVVDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERP
  ILGQNDNKSKTLKCSTLLVVGDNSPAVEAVVECNSRLNPINTTLLKMADCGGLPQVVQPG
  KLTEAFKYFLQGMGYIPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCE
  SPDVLDRHQTMEVSC
• Tissue Specificity: Ubiquitous. Highly expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Stomach cancer	DISKIJSX	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein NDRG3 (NDRG3).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein NDRG3 (NDRG3).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein NDRG3 (NDRG3).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein NDRG3 (NDRG3).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein NDRG3 (NDRG3).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein NDRG3 (NDRG3).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein NDRG3 (NDRG3).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein NDRG3 (NDRG3).	[16]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Protein NDRG3 (NDRG3).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein NDRG3 (NDRG3).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein NDRG3 (NDRG3).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein NDRG3 (NDRG3).	[23]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Protein NDRG3 (NDRG3).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein NDRG3 (NDRG3).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein NDRG3 (NDRG3).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein NDRG3 (NDRG3).	[21]

References

• [1] NDRG3 is an androgen regulated and prostate enriched gene that promotes in vitro and in vivo prostate cancer cell growth.Int J Cancer. 2009 Feb 1;124(3):521-30. doi: 10.1002/ijc.23961.
• [2] Clinical significance of NDRG3 in patients with breast cancer.Future Oncol. 2017 May;13(11):961-969. doi: 10.2217/fon-2016-0457. Epub 2017 Feb 27.
• [3] Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3.Neurochem Res. 2017 Feb;42(2):446-454. doi: 10.1007/s11064-016-2091-x. Epub 2016 Nov 4.
• [4] SNHG20/miR-140-5p/NDRG3 axis contributes to 5-fluorouracil resistance in gastric cancer.Oncol Lett. 2019 Aug;18(2):1337-1343. doi: 10.3892/ol.2019.10439. Epub 2019 Jun 5.
• [5] NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma.Biosci Rep. 2018 Dec 7;38(6):BSR20180907. doi: 10.1042/BSR20180907. Print 2018 Dec 21.
• [6] High expression of NDRG3 associates with unfavorable overall survival in non-small cell lung cancer.Cancer Biomark. 2018 Feb 6;21(2):461-469. doi: 10.3233/CBM-170711.
• [7] NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors.Exp Mol Med. 2018 May 14;50(5):1-13. doi: 10.1038/s12276-018-0089-y.
• [8] NDRG3 facilitates colorectal cancer metastasis through activating Src phosphorylation.Onco Targets Ther. 2018 May 15;11:2843-2852. doi: 10.2147/OTT.S156814. eCollection 2018.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [14] 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.
• [15] 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.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [18] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [23] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.