Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUE809X)

• DOT Name: Coiled-coil domain-containing protein 3 (CCDC3)
• Synonyms: Fat/vessel-derived secretory protein; Favine
• Gene Name: CCDC3
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Acute myelogenous leukaemia
• UniProt ID: CCDC3_HUMAN
• Sequence:
  MLRQLLLAALCLAGPPAPARACQLPSEWRPLSEGCRAELAETIVYARVLALHPEAPGLYN
  HLPWQYHAGQGGLFYSAEVEMLCDQAWGSMLEVPAGSRLNLTGLGYFSCHSHTVVQDYSY
  FFFLRMDENYNLLPHGVNFQDAIFPDTQENRRMFSSLFQFSNCSQGQQLATFSSDWEIQE
  DSRLMCSSVQKALFEEEDHVKKLQQKVATLEKRNRQLRERVKKVKRSLRQARKKGRHLEL
  ANQKLSEKLAAGALPHINARGPVRPPYLRG
• Function: Negatively regulates TNF-alpha-induced pro-inflammatory response in endothelial cells (ECs) via inhibition of TNF-alpha-induced NF-kappaB activation in ECs. Positively regulates lipid accumulation in adipose cells.
• Tissue Specificity: Expressed in umbilical vein endothelial cells (HUVEC), and at lower levels in aortic smooth muscle cells (HASMC).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[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 3 (CCDC3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Coiled-coil domain-containing protein 3 (CCDC3).	[10]

9 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 3 (CCDC3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Coiled-coil domain-containing protein 3 (CCDC3).	[13]

References

• [1] Regulatory effects of CCDC3 on proliferation, migration, invasion and EMT of human cervical cancer cells.Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3217-3224. doi: 10.26355/eurrev_201904_17680.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] 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.
• [11] 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.
• [12] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.