Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5YQ0R0)

• DOT Name: Coiled-coil domain-containing protein 86 (CCDC86)
• Synonyms: Cytokine-induced protein with coiled-coil domain
• Gene Name: CCDC86
• Related Disease:
  B-cell lymphoma
  Schizophrenia
• UniProt ID: CCD86_HUMAN
• PDB ID: 8FL0; 8FL2; 8FL3; 8FL4; 8INK; 8IPD; 8IPX; 8IPY; 8IR1; 8IR3
• Pfam ID: PF03879
• Sequence:
  MDTPLRRSRRLGGLRPESPESLTSVSRTRRALVEFESNPEETREPGSPPSVQRAGLGSPE
  RPPKTSPGSPRLQQGAGLESPQGQPEPGAASPQRQQDLHLESPQRQPEYSPESPRCQPKP
  SEEAPKCSQDQGVLASELAQNKEELTPGAPQHQLPPVPGSPEPYPGQQAPGPEPSQPLLE
  LTPRAPGSPRGQHEPSKPPPAGETVTGGFGAKKRKGSSSQAPASKKLNKEELPVIPKGKP
  KSGRVWKDRSKKRFSQMLQDKPLRTSWQRKMKERQERKLAKDFARHLEEEKERRRQEKKQ
  RRAENLKRRLENERKAEVVQVIRNPAKLKRAKKKQLRSIEKRDTLALLQKQPPQQPAAKI

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]

18 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 86 (CCDC86).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[18]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Coiled-coil domain-containing protein 86 (CCDC86).	[19]

2 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 affects the phosphorylation of Coiled-coil domain-containing protein 86 (CCDC86).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Coiled-coil domain-containing protein 86 (CCDC86).	[17]

References

• [1] Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers. EMBO Mol Med. 2013 Aug;5(8):1180-95. doi: 10.1002/emmm.201202034. Epub 2013 Jul 4.
• [2] Expression and differential response to haloperidol treatment of Cyclon/CCDC86 mRNA in schizophrenia patients.Neurochem Int. 2013 May;62(6):870-2. doi: 10.1016/j.neuint.2013.02.017. Epub 2013 Feb 21.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] 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.
• [11] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [12] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] 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.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.