Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT43MI0R)

• DOT Name: Coiled-coil domain-containing protein 69 (CCDC69)
• Gene Name: CCDC69
• Related Disease: Chronic obstructive pulmonary disease
• UniProt ID: CCD69_HUMAN
• Sequence:
  MGCRHSRLSSCKPPKKKRQEPEPEQPPRPEPHELGPLNGDTAITVQLCASEEAERHQKDI
  TRILQQHEEEKKKWAQQVEKERELELRDRLDEQQRVLEGKNEEALQVLRASYEQEKEALT
  HSFREASSTQQETIDRLTSQLEAFQAKMKRVEESILSRNYKKHIQDYGSPSQFWEQELES
  LHFVIEMKNERIHELDRRLILMETVKEKNLILEEKITTLQQENEDLHVRSRNQVVLSRQL
  SEDLLLTREALEKEVQLRRQLQQEKEELLYRVLGANASPAFPLAPVTPTEVSFLAT
• Function: May act as a scaffold to regulate the recruitment and assembly of spindle midzone components. Required for the localization of AURKB and PLK1 to the spindle midzone.
• Tissue Specificity: Highly expressed in duodenum, esophagus, pancreas, prostate, salivary gland, thymus and urinary bladder.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]

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 Coiled-coil domain-containing protein 69 (CCDC69).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Coiled-coil domain-containing protein 69 (CCDC69).	[15]

References

• [1] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [12] 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.
• [13] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.