Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM03SME)

• DOT Name: Anaphase-promoting complex subunit 10 (ANAPC10)
• Synonyms: APC10; Cyclosome subunit 10
• Gene Name: ANAPC10
• Related Disease:
  Advanced cancer
  Atrial fibrillation
  Colorectal carcinoma
  Epithelial ovarian cancer
  Non-small-cell lung cancer
  Oral cancer
  Ovarian cancer
  Ovarian neoplasm
  Neoplasm
  Squamous cell carcinoma
• UniProt ID: APC10_HUMAN
• PDB ID: 1JHJ; 4UI9; 5A31; 5G04; 5G05; 5KHR; 5KHU; 5L9T; 5L9U; 5LCW; 6Q6G; 6Q6H; 6TLJ; 6TM5; 6TNT; 7QE7; 8PKP; 8TAR; 8TAU
• Pfam ID: PF03256
• Sequence:
  MTTPNKTPPGADPKQLERTGTVREIGSQAVWSLSSCKPGFGVDQLRDDNLETYWQSDGSQ
  PHLVNIQFRRKTTVKTLCIYADYKSDESYTPSKISVRVGNNFHNLQEIRQLELVEPSGWI
  HVPLTDNHKKPTRTFMIQIAVLANHQNGRDTHMRQIKIYTPVEESSIGKFPRCTTIDFMM
  YRSIR
• Function: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  Ubiquitin mediated proteolysis (hsa04120)
  Progesterone-mediated oocyte maturation (hsa04914)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway:
  APC/C (R-HSA-174048)
  Autodegradation of Cdh1 by Cdh1 (R-HSA-174084)
  APC/C (R-HSA-174154)
  APC/C (R-HSA-174178)
  Cdc20 (R-HSA-174184)
  Conversion from APC/C (R-HSA-176407)
  Regulation of APC/C activators between G1/S and early anaphase (R-HSA-176408)
  APC/C (R-HSA-176409)
  Phosphorylation of the APC/C (R-HSA-176412)
  APC-Cdc20 mediated degradation of Nek2A (R-HSA-179409)
  Separation of Sister Chromatids (R-HSA-2467813)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  Assembly of the pre-replicative complex (R-HSA-68867)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  Transcriptional Regulation by VENTX (R-HSA-8853884)
  Aberrant regulation of mitotic exit in cancer due to RB1 defects (R-HSA-9687136)
  Antigen processing (R-HSA-983168)
  Inactivation of APC/C via direct inhibition of the APC/C complex (R-HSA-141430)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Oral cancer	DISLD42D	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Altered Expression	[6]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[14]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Anaphase-promoting complex subunit 10 (ANAPC10).	[17]

References

• [1] A novel function of anaphase promoting complex subunit 10 in tumor progression in non-small cell lung cancer.Cell Cycle. 2019 May;18(9):1019-1032. doi: 10.1080/15384101.2019.1609830. Epub 2019 Apr 25.
• [2] Effectiveness of the Chest Strap Electrocardiogram to Detect Atrial Fibrillation.Am J Cardiol. 2019 May 15;123(10):1643-1648. doi: 10.1016/j.amjcard.2019.02.028. Epub 2019 Feb 23.
• [3] Modulation of CDK2-AP1 (p12(DOC-1)) expression in human colorectal cancer.Oncogene. 2005 May 19;24(22):3657-68. doi: 10.1038/sj.onc.1208378.
• [4] Molecular cloning of differentially expressed genes in human epithelial ovarian cancer.Gynecol Oncol. 1994 Feb;52(2):247-52. doi: 10.1006/gyno.1994.1040.
• [5] DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells.Cell Rep. 2017 Jul 5;20(1):61-75. doi: 10.1016/j.celrep.2017.06.020.
• [6] Sensitivity to TOP2 targeting chemotherapeutics is regulated by Oct1 and FILIP1L.PLoS One. 2012;7(8):e42921. doi: 10.1371/journal.pone.0042921. Epub 2012 Aug 10.
• [7] Risk estimation for a malignant transformation of oral lesions by S100A7 and Doc-1 gene expression.Cancer Invest. 2011 Aug;29(7):478-84. doi: 10.3109/07357907.2011.597813.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [12] 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.
• [13] 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.
• [14] Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer. 2007 Jun;14(2):305-15. doi: 10.1677/ERC-06-0003.
• [15] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.