Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4KF6TL)

• DOT Name: Coiled-coil domain-containing protein 68 (CCDC68)
• Synonyms: Cutaneous T-cell lymphoma-associated antigen se57-1; CTCL-associated antigen se57-1
• Gene Name: CCDC68
• Related Disease:
  Narcolepsy
  Neoplasm
  Schizophrenia
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
• UniProt ID: CCD68_HUMAN
• Sequence:
  MTTVTVTTEIPPRDKMEDNSALYESTSAHIIEETEYVKKIRTTLQKIRTQMFKDEIRHDS
  TNHKLDAKHCGNLQQGSDSEMDPSCCSLDLLMKKIKGKDLQLLEMNKENEVLKIKLQASR
  EAGAAALRNVAQRLFENYQTQSEEVRKKQEDSKQLLQVNKLEKEQKLKQHVENLNQVAEK
  LEEKHSQITELENLVQRMEKEKRTLLERKLSLENKLLQLKSSATYGKSCQDLQREISILQ
  EQISHLQFVIHSQHQNLRSVIQEMEGLKNNLKEQDKRIENLREKVNILEAQNKELKTQVA
  LSSETPRTKVSKAVSTSELKTEGVSPYLMLIRLRK
• Function: Centriolar protein required for centriole subdistal appendage assembly and microtubule anchoring in interphase cells. Together with CCDC120, cooperate with subdistal appendage components ODF2, NIN and CEP170 for hierarchical subdistal appendage assembly.
• Tissue Specificity: Expressed in bone marrow, colon, small intestine, spleen, testis, trachea and cutaneous T-cell lymphoma (CTCL).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[2]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Coiled-coil domain-containing protein 68 (CCDC68).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Coiled-coil domain-containing protein 68 (CCDC68).	[10]

13 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 Coiled-coil domain-containing protein 68 (CCDC68).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[13]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Coiled-coil domain-containing protein 68 (CCDC68).	[13]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role in pancreatic ductal adenocarcinoma.Oncogene. 2015 Aug 6;34(32):4238-47. doi: 10.1038/onc.2014.357. Epub 2014 Nov 10.
• [3] 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.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [11] 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.
• [12] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.