Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMY5KAE)

• DOT Name: Centrosomal protein of 70 kDa (CEP70)
• Synonyms: Cep70; p10-binding protein
• Gene Name: CEP70
• Related Disease:
  Anorexia nervosa cachexia
  Chronic obstructive pulmonary disease
  Pancreatic cancer
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Osteoarthritis
  Rheumatoid arthritis
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: CEP70_HUMAN
• Sequence:
  MFPVAPKPQDSSQPSDRLMTEKQQEEAEWESINVLLMMHGLKPLSLVKRTDLKDLIIFDK
  QSSQRMRQNLKLLVEETSCQQNMIQELIETNQQLRNELQLEQSRAANQEQRANDLEQIME
  SVKSKIGELEDESLSRACHQQNKIKDLQKEQKTLQVKCQHYKKKRTEQEETIASLQMEVC
  RLKKEEEDRIVTQNRVFAYLCKRVPHTVLDRQLLCLIDYYESKIRKIHTQRQYKEDESQS
  EEENDYRNLDASPTYKGLLMSLQNQLKESKSKIDALSSEKLNLQKDLETRPTQHELRLYK
  QQVKKLEKALKKNVKLQELINHKKAEDTEKKDEPSKYNQQQALIDQRYFQVLCSINSIIH
  NPRAPVIIYKQTKGGVQNFNKDLVQDCGFEHLVPVIEMWADQLTSLKDLYKSLKTLSAEL
  VPWLNLKKQDENEGIKVEDLLFIVDTMLEEVENKEKDSNMPHFQTLQAIVSHFQKLFDVP
  SLNGVYPRMNEVYTRLGEMNNAVRNLQELLELDSSSSLCVLVSTVGKLCRLINEDVNEQV
  MQVLGPEDLQSIIYKLEEHEEFFPAFQAFTNDLLEILEIDDLDAIVPAVKKLKVLSY
• Function: Plays a role in the organization of both preexisting and nascent microtubules in interphase cells. During mitosis, required for the organization and orientation of the mitotic spindle.
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[3]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[6]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[7]
Rheumatoid arthritis	DISTSB4J	moderate	Altered Expression	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[8]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]

1 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 Centrosomal protein of 70 kDa (CEP70).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centrosomal protein of 70 kDa (CEP70).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Centrosomal protein of 70 kDa (CEP70).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Centrosomal protein of 70 kDa (CEP70).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Centrosomal protein of 70 kDa (CEP70).	[17]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Centrosomal protein of 70 kDa (CEP70).	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Centrosomal protein of 70 kDa (CEP70).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Centrosomal protein of 70 kDa (CEP70).	[24]

References

• [1] Dysfunction of inflammatory pathways in adolescent female patients with anorexia nervosa.Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jan 10;96:109727. doi: 10.1016/j.pnpbp.2019.109727. Epub 2019 Aug 6.
• [2] The genetics of smoking in individuals with chronic obstructive pulmonary disease.Respir Res. 2018 Apr 10;19(1):59. doi: 10.1186/s12931-018-0762-7.
• [3] Cep70 overexpression stimulates pancreatic cancer by inducing centrosome abnormality and microtubule disorganization.Sci Rep. 2016 Feb 19;6:21263. doi: 10.1038/srep21263.
• [4] A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo.Leukemia. 2017 Aug;31(8):1743-1751. doi: 10.1038/leu.2016.388. Epub 2016 Dec 27.
• [5] Anti-PSMA/CD3 Bispecific Antibody Delivery and Antitumor Activity Using a Polymeric Depot Formulation.Mol Cancer Ther. 2018 Sep;17(9):1927-1940. doi: 10.1158/1535-7163.MCT-17-1138. Epub 2018 Jun 11.
• [6] Nanoparticles That Reshape the Tumor Milieu Create a Therapeutic Window for Effective T-cell Therapy in Solid Malignancies.Cancer Res. 2018 Jul 1;78(13):3718-3730. doi: 10.1158/0008-5472.CAN-18-0306. Epub 2018 May 14.
• [7] Decoy receptor 3 down-regulates centrosomal protein 70kDa specifically in rheumatoid synovial fibroblasts.Mod Rheumatol. 2018 Mar;28(2):287-292. doi: 10.1080/14397595.2017.1341593. Epub 2017 Jul 11.
• [8] Discovery of Centrosomal Protein 70 as an Important Player in the Development and Progression of Breast Cancer.Am J Pathol. 2017 Mar;187(3):679-688. doi: 10.1016/j.ajpath.2016.11.005. Epub 2017 Jan 5.
• [9] 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.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [17] 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.
• [18] 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.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] 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.
• [22] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [24] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.