Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4SKM1W)

• DOT Name: Coiled-coil domain-containing protein 9 (CCDC9)
• Gene Name: CCDC9
• UniProt ID: CCDC9_HUMAN
• Pfam ID: PF15266
• Sequence:
  MAATLDLKSKEEKDAELDKRIEALRRKNEALIRRYQEIEEDRKKAELEGVAVTAPRKGRS
  VEKENVAVESEKNLGPSRRSPGTPRPPGASKGGRTPPQQGGRAGMGRASRSWEGSPGEQP
  RGGGAGGRGRRGRGRGSPHLSGAGDTSISDRKSKEWEERRRQNIEKMNEEMEKIAEYERN
  QREGVLEPNPVRNFLDDPRRRSGPLEESERDRREESRRHGRNWGGPDFERVRCGLEHERQ
  GRRAGLGSAGDMTLSMTGRERSEYLRWKQEREKIDQERLQRHRKPTGQWRREWDAEKTDG
  MFKDGPVPAHEPSHRYDDQAWARPPKPPTFGEFLSQHKAEASSRRRRKSSRPQAKAAPRA
  YSDHDDRWETKEGAASPAPETPQPTSPETSPKETPMQPPEIPAPAHRPPEDEGEENEGEE
  DEEWEDISEDEEEEEIEVEEGDEEEPAQDHQAPEAAPTGIPCSEQAHGVPFSPEEPLLEP
  QAPGTPSSPFSPPSGHQPVSDWGEEVELNSPRTTHLAGALSPGEAWPFESV
• Function: Probable component of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Coiled-coil domain-containing protein 9 (CCDC9).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Coiled-coil domain-containing protein 9 (CCDC9).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Coiled-coil domain-containing protein 9 (CCDC9).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Coiled-coil domain-containing protein 9 (CCDC9).	[10]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Coiled-coil domain-containing protein 9 (CCDC9).	[11]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Coiled-coil domain-containing protein 9 (CCDC9).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coiled-coil domain-containing protein 9 (CCDC9).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 9 (CCDC9).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Coiled-coil domain-containing protein 9 (CCDC9).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coiled-coil domain-containing protein 9 (CCDC9).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Coiled-coil domain-containing protein 9 (CCDC9).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Coiled-coil domain-containing protein 9 (CCDC9).	[8]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] 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.
• [11] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.