Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKB9C3S)

• DOT Name: ATP-dependent RNA helicase DDX18 (DDX18)
• Synonyms: EC 3.6.4.13; DEAD box protein 18; Myc-regulated DEAD box protein; MrDb
• Gene Name: DDX18
• Related Disease:
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Advanced cancer
  Hepatitis
  Hepatitis A virus infection
  Hepatitis C virus infection
  Osteoarthritis
• UniProt ID: DDX18_HUMAN
• PDB ID: 3LY5; 8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF13959 ; PF00271
• Sequence:
  MSHLPMKLLRKKIEKRNLKLRQRNLKFQGASNLTLSETQNGDVSEETMGSRKVKKSKQKP
  MNVGLSETQNGGMSQEAVGNIKVTKSPQKSTVLTNGEAAMQSSNSESKKKKKKKRKMVND
  AEPDTKKAKTENKGKSEEESAETTKETENNVEKPDNDEDESEVPSLPLGLTGAFEDTSFA
  SLCNLVNENTLKAIKEMGFTNMTEIQHKSIRPLLEGRDLLAAAKTGSGKTLAFLIPAVEL
  IVKLRFMPRNGTGVLILSPTRELAMQTFGVLKELMTHHVHTYGLIMGGSNRSAEAQKLGN
  GINIIVATPGRLLDHMQNTPGFMYKNLQCLVIDEADRILDVGFEEELKQIIKLLPTRRQT
  MLFSATQTRKVEDLARISLKKEPLYVGVDDDKANATVDGLEQGYVVCPSEKRFLLLFTFL
  KKNRKKKLMVFFSSCMSVKYHYELLNYIDLPVLAIHGKQKQNKRTTTFFQFCNADSGTLL
  CTDVAARGLDIPEVDWIVQYDPPDDPKEYIHRVGRTARGLNGRGHALLILRPEELGFLRY
  LKQSKVPLSEFDFSWSKISDIQSQLEKLIEKNYFLHKSAQEAYKSYIRAYDSHSLKQIFN
  VNNLNLPQVALSFGFKVPPFVDLNVNSNEGKQKKRGGGGGFGYQKTKKVEKSKIFKHISK
  KSSDSRQFSH
• Function: Probable RNA-dependent helicase.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Hepatitis	DISXXX35	Strong	Biomarker	[3]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[4]
Osteoarthritis	DIS05URM	Strong	Biomarker	[5]

15 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 ATP-dependent RNA helicase DDX18 (DDX18).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[13]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[14]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ATP-dependent RNA helicase DDX18 (DDX18).	[20]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of ATP-dependent RNA helicase DDX18 (DDX18).	[15]

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 decreases the phosphorylation of ATP-dependent RNA helicase DDX18 (DDX18).	[17]

References

• [1] Ddx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML.Blood. 2011 Jul 28;118(4):903-15. doi: 10.1182/blood-2010-11-318022. Epub 2011 Jun 7.
• [2] Aberrant splice variants of HAS1 (Hyaluronan Synthase 1) multimerize with and modulate normally spliced HAS1 protein: a potential mechanism promoting human cancer.J Biol Chem. 2009 Jul 10;284(28):18840-50. doi: 10.1074/jbc.M109.013813. Epub 2009 May 18.
• [3] The Hepatitis Aggressiveness Score (HAS): a novel classification system for post-liver transplantation recurrent hepatitis C.Am J Surg Pathol. 2013 Jan;37(1):104-13. doi: 10.1097/PAS.0b013e31826a92ac.
• [4] PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases.Int J Cancer. 2019 Feb 1;144(3):533-544. doi: 10.1002/ijc.31910. Epub 2018 Nov 9.
• [5] Hyaluronan synthases, hyaluronan, and its CD44 receptor in tissue around loosened total hip prostheses.J Pathol. 2001 Jul;194(3):384-90. doi: 10.1002/1096-9896(200107)194:3<384::AID-PATH896>3.0.CO;2-8.
• [6] 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.
• [7] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [8] 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.
• [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] 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.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [14] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [15] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [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] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.