Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1FFWKC)

• DOT Name: Cell division cycle-associated 7-like protein (CDCA7L)
• Synonyms: Protein JPO2; Transcription factor RAM2
• Gene Name: CDCA7L
• Related Disease:
  Anaplastic astrocytoma
  Breast carcinoma
  Burkitt lymphoma
  Glioma
  Hepatocellular carcinoma
  Medulloblastoma
  Multiple endocrine neoplasia type 1
  Myocardial infarction
  Neoplasm
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Glioblastoma multiforme
• UniProt ID: CDA7L_HUMAN
• PDB ID: 5YI9; 6EMO
• Pfam ID: PF10497
• Sequence:
  MELATRYQIPKEVADIFNAPSDDEEFVGFRDDVPMETLSSEESCDSFDSLESGKQQDVRF
  HSKYFTEELRRIFIEDTDSETEDFAGFTQSDLNGKTNPEVMVVESDLSDDGKASLVSEEE
  EDEEEDKATPRRSRSRRSSIGLRVAFQFPTKKLANKPDKNSSSEQLFSSARLQNEKKTIL
  ERKKDCRQVIQREDSTSESEDDSRDESQESSDALLKRTMNIKENKAMLAQLLAELNSMPD
  FFPVRTPTSASRKKTVRRAFSEGQITRRMNPTRSARPPEKFALENFTVSAAKFAEEFYSF
  RRRKTIGGKCREYRRRHRISSFRPVEDITEEDLENVAITVRDKIYDKVLGNTCHQCRQKT
  IDTKTVCRNQGCCGVRGQFCGPCLRNRYGEDVRSALLDPDWVCPPCRGICNCSYCRKRDG
  RCATGILIHLAKFYGYDNVKEYLESLQKELVEDN
• Function: Plays a role in transcriptional regulation as a repressor that inhibits monoamine oxidase A (MAOA) activity and gene expression by binding to the promoter. Plays an important oncogenic role in mediating the full transforming effect of MYC in medulloblastoma cells. Involved in apoptotic signaling pathways; May act downstream of P38-kinase and BCL-2, but upstream of CASP3/caspase-3 as well as CCND1/cyclin D1 and E2F1.
• Tissue Specificity: Ubiquitous. Overexpressed in medulloblastoma.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anaplastic astrocytoma	DISSBE0K	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[5]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Biomarker	[6]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[8]
Prostate cancer	DISF190Y	Strong	Altered Expression	[9]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[10]

16 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 Cell division cycle-associated 7-like protein (CDCA7L).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[17]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[18]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[19]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[23]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[27]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cell division cycle-associated 7-like protein (CDCA7L).	[29]

4 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 Cell division cycle-associated 7-like protein (CDCA7L).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Cell division cycle-associated 7-like protein (CDCA7L).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cell division cycle-associated 7-like protein (CDCA7L).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Cell division cycle-associated 7-like protein (CDCA7L).	[28]

References

• [1] Cell division cycle associated 7 like predicts unfavorable prognosis and promotes invasion in glioma.Pathol Res Pract. 2019 Jan;215(1):50-56. doi: 10.1016/j.prp.2018.10.023. Epub 2018 Oct 24.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] Regulation of c-fgr proto-oncogene expression in Epstein-Barr virus infected B-cell lines.Int J Cancer. 1990 Feb 15;45(2):342-6. doi: 10.1002/ijc.2910450222.
• [4] CDCA7L promotes hepatocellular carcinoma progression by regulating the cell cycle.Int J Oncol. 2013 Dec;43(6):2082-90. doi: 10.3892/ijo.2013.2142. Epub 2013 Oct 17.
• [5] Silencing of thrombospondin-1 is critical for myc-induced metastatic phenotypes in medulloblastoma.Cancer Res. 2010 Oct 15;70(20):8199-210. doi: 10.1158/0008-5472.CAN-09-4562. Epub 2010 Sep 28.
• [6] Distinct genome-wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors.Cancer. 2019 Apr 15;125(8):1247-1257. doi: 10.1002/cncr.31930. Epub 2019 Jan 8.
• [7] Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats.Biomaterials. 2016 Aug;97:164-75. doi: 10.1016/j.biomaterials.2016.04.025. Epub 2016 Apr 26.
• [8] Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression.Nat Commun. 2016 Nov 24;7:13656. doi: 10.1038/ncomms13656.
• [9] R1 Regulates Prostate Tumor Growth and Progression By Transcriptional Suppression of the E3 Ligase HUWE1 to Stabilize c-Myc.Mol Cancer Res. 2018 Dec;16(12):1940-1951. doi: 10.1158/1541-7786.MCR-16-0346. Epub 2018 Jul 24.
• [10] CDCA7L promotes glioma proliferation by targeting CCND1 and predicts an unfavorable prognosis.Mol Med Rep. 2019 Aug;20(2):1149-1156. doi: 10.3892/mmr.2019.10349. Epub 2019 Jun 5.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] 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.
• [13] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] 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.
• [16] 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.
• [17] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [20] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [24] 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.
• [25] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [26] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [27] 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.
• [28] 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.
• [29] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.