Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8DS3CX)

• DOT Name: NudC domain-containing protein 1 (NUDCD1)
• Synonyms: Chronic myelogenous leukemia tumor antigen 66; Tumor antigen CML66
• Gene Name: NUDCD1
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Acute myelogenous leukaemia
  Advanced cancer
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Clear cell renal carcinoma
  Colorectal carcinoma
  leukaemia
  Lung cancer
  Lung carcinoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Leukemia
• UniProt ID: NUDC1_HUMAN
• Pfam ID: PF04969
• Sequence:
  MEVAANCSLRVKRPLLDPRFEGYKLSLEPLPCYQLELDAAVAEVKLRDDQYTLEHMHAFG
  MYNYLHCDSWYQDSVYYIDTLGRIMNLTVMLDTALGKPREVFRLPTDLTACDNRLCASIH
  FSSSTWVTLSDGTGRLYVIGTGERGNSASEKWEIMFNEELGDPFIIIHSISLLNAEEHSI
  ATLLLRIEKEELDMKGSGFYVSLEWVTISKKNQDNKKYEIIKRDILRGKSVPHYAAIEPD
  GNGLMIVSYKSLTFVQAGQDLEENMDEDISEKIKEPLYYWQQTEDDLTVTIRLPEDSTKE
  DIQIQFLPDHINIVLKDHQFLEGKLYSSIDHESSTWIIKESNSLEISLIKKNEGLTWPEL
  VIGDKQGELIRDSAQCAAIAERLMHLTSEELNPNPDKEKPPCNAQELEECDIFFEESSSL
  CRFDGNTLKTTHVVNLGSNQYLFSVIVDPKEMPCFCLRHDVDALLWQPHSSKQDDMWEHI
  ATFNALGYVQASKRDKKFFACAPNYSYAALCECLRRVFIYRQPAPMSTVLYNRKEGRQVG
  QVAKQQVASLETNDPILGFQATNERLFVLTTKNLFLIKVNTEN
• Tissue Specificity: Isoform 1 is specifically expressed in leukemias and a variety of solid tumor cell lines and is also detected in testis and heart. Isoform 2 is predominantly expressed in testis and weakly expressed in tumor cells.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[1]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
leukaemia	DISS7D1V	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[6]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[4]
Leukemia	DISNAKFL	Limited	Altered Expression	[2]

14 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 NudC domain-containing protein 1 (NUDCD1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of NudC domain-containing protein 1 (NUDCD1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NudC domain-containing protein 1 (NUDCD1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NudC domain-containing protein 1 (NUDCD1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NudC domain-containing protein 1 (NUDCD1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of NudC domain-containing protein 1 (NUDCD1).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of NudC domain-containing protein 1 (NUDCD1).	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of NudC domain-containing protein 1 (NUDCD1).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of NudC domain-containing protein 1 (NUDCD1).	[16]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of NudC domain-containing protein 1 (NUDCD1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of NudC domain-containing protein 1 (NUDCD1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of NudC domain-containing protein 1 (NUDCD1).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of NudC domain-containing protein 1 (NUDCD1).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of NudC domain-containing protein 1 (NUDCD1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of NudC domain-containing protein 1 (NUDCD1).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of NudC domain-containing protein 1 (NUDCD1).	[22]

References

• [1] OVA66 increases cell growth, invasion and survival via regulation of IGF-1R-MAPK signaling in human cancer cells.Carcinogenesis. 2014 Jul;35(7):1573-81. doi: 10.1093/carcin/bgu070. Epub 2014 Mar 25.
• [2] Graft-versus-leukemia target antigens in chronic myelogenous leukemia are expressed on myeloid progenitor cells.Clin Cancer Res. 2005 Jun 15;11(12):4504-11. doi: 10.1158/1078-0432.CCR-05-0036.
• [3] OVA66 promotes tumour angiogenesis and progression through enhancing autocrine VEGF-VEGFR2 signalling.EBioMedicine. 2019 Mar;41:156-166. doi: 10.1016/j.ebiom.2019.02.051. Epub 2019 Mar 1.
• [4] NudCD1 affects renal cell carcinoma through regulating LIS1/Dynein signaling pathway.Am J Transl Res. 2018 Feb 15;10(2):519-524. eCollection 2018.
• [5] NUDCD1 promotes metastasis through inducing EMT and inhibiting apoptosis in colorectal cancer.Am J Cancer Res. 2018 May 1;8(5):810-823. eCollection 2018.
• [6] CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia.Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7492-7. doi: 10.1073/pnas.131590998.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [16] 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.
• [17] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [18] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] 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.