Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNSGYK1)

• DOT Name: DDB1- and CUL4-associated factor 11 (DCAF11)
• Synonyms: WD repeat-containing protein 23
• Gene Name: DCAF11
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: DCA11_HUMAN
• Pfam ID: PF00400
• Sequence:
  MGSRNSSSAGSGSGDPSEGLPRRGAGLRRSEEEEEEDEDVDLAQVLAYLLRRGQVRLVQG
  GGAANLQFIQALLDSEEENDRAWDGRLGDRYNPPVDATPDTRELEFNEIKTQVELATGQL
  GLRRAAQKHSFPRMLHQRERGLCHRGSFSLGEQSRVISHFLPNDLGFTDSYSQKAFCGIY
  SKDGQIFMSACQDQTIRLYDCRYGRFRKFKSIKARDVGWSVLDVAFTPDGNHFLYSSWSD
  YIHICNIYGEGDTHTALDLRPDERRFAVFSIAVSSDGREVLGGANDGCLYVFDREQNRRT
  LQIESHEDDVNAVAFADISSQILFSGGDDAICKVWDRRTMREDDPKPVGALAGHQDGITF
  IDSKGDARYLISNSKDQTIKLWDIRRFSSREGMEASRQAATQQNWDYRWQQVPKKAWRKL
  KLPGDSSLMTYRGHGVLHTLIRCRFSPIHSTGQQFIYSGCSTGKVVVYDLLSGHIVKKLT
  NHKACVRDVSWHPFEEKIVSSSWDGNLRLWQYRQAEYFQDDMPESEECASAPAPVPQSST
  PFSSPQ
• Function: May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Strong	Biomarker	[1]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[1]

10 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 DDB1- and CUL4-associated factor 11 (DCAF11).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[8]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DDB1- and CUL4-associated factor 11 (DCAF11).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DDB1- and CUL4-associated factor 11 (DCAF11).	[12]

References

• [1] Small molecule TSC01682 inhibits osteosarcoma cell growth by specifically disrupting the CUL4B-DDB1 interaction and decreasing the ubiquitination of CRL4B E3 ligase substrates.Am J Cancer Res. 2019 Sep 1;9(9):1857-1870. eCollection 2019.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] 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.