Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT60PR7J)

• DOT Name: DDB1- and CUL4-associated factor 16 (DCAF16)
• Gene Name: DCAF16
• UniProt ID: DCA16_HUMAN
• PDB ID: 8G46; 8OV6
• Pfam ID: PF15349
• Sequence:
  MGPRNPSPDHLSESESEEEENISYLNESSGEEWDSSEEEDSMVPNLSPLESLAWQVKCLL
  KYSTTWKPLNPNSWLYHAKLLDPSTPVHILREIGLRLSHCSHCVPKLEPIPEWPPLASCG
  VPPFQKPLTSPSRLSRDHATLNGALQFATKQLSRTLSRATPIPEYLKQIPNSCVSGCCCG
  WLTKTVKETTRTEPINTTYSYTDFQKAVNKLLTASL
• Function: Functions as a substrate recognition component for CUL4-DDB1 E3 ubiquitin-protein ligase complex, which mediates ubiquitination and proteasome-dependent degradation of nuclear proteins.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

9 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 DDB1- and CUL4-associated factor 16 (DCAF16).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[5]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[8]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DDB1- and CUL4-associated factor 16 (DCAF16).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of DDB1- and CUL4-associated factor 16 (DCAF16).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] 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.
• [9] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [10] 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.