Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH48438)

• DOT Name: Probable ATP-dependent RNA helicase DDX10 (DDX10)
• Synonyms: EC 3.6.4.13; DEAD box protein 10
• Gene Name: DDX10
• Related Disease:
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Childhood myelodysplastic syndrome
  Epithelial ovarian cancer
  Neoplasm
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Acute myelogenous leukaemia
  Breast carcinoma
  Myelodysplastic syndrome
• UniProt ID: DDX10_HUMAN
• PDB ID: 2PL3
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF13959 ; PF00271
• Sequence:
  MGKTANSPGSGARPDPVRSFNRWKKKHSHRQNKKKQLRKQLKKPEWQVERESISRLMQNY
  EKINVNEITRFSDFPLSKKTLKGLQEAQYRLVTEIQKQTIGLALQGKDVLGAAKTGSGKT
  LAFLVPVLEALYRLQWTSTDGLGVLIISPTRELAYQTFEVLRKVGKNHDFSAGLIIGGKD
  LKHEAERINNINILVCTPGRLLQHMDETVSFHATDLQMLVLDEADRILDMGFADTMNAVI
  ENLPKKRQTLLFSATQTKSVKDLARLSLKNPEYVWVHEKAKYSTPATLEQNYIVCELQQK
  ISVLYSFLRSHLKKKSIVFFSSCKEVQYLYRVFCRLRPGVSILALHGRQQQMRRMEVYNE
  FVRKRAAVLFATDIAARGLDFPAVNWVLQFDCPEDANTYIHRAGRTARYKEDGEALLILL
  PSEKAMVQQLLQKKVPVKEIKINPEKLIDVQKKLESILAQDQDLKERAQRCFVSYVRSVY
  LMKDKEVFDVSKLPIPEYALSLGLAVAPRVRFLQKMQKQPTKELVRSQADKVIEPRAPSL
  TNDEVEEFRAYFNEKMSILQKGGKRLEGTEHRQDNDTGNEEQEEEEDDEEEMEEKLAKAK
  GSQAPSLPNTSEAQKIKEVPTQFLDRDEEEEDADFLKVKRHNVFGLDLKDEKTLQKKEPS
  KSSIKKKMTKVAEAKKVMKRNFKVNKKITFTDEGELVQQWPQMQKSAIKDAEEDDDTGGI
  NLHKAKERLQEEDKFDKEEYRKKIKAKHREKRLKEREARREANKRQAKAKDEEEAFLDWS
  DDDDDDDDGFDPSTLPDPDKYRSSEDSDSEDMENKISDTKKKQGMKKRSNSEVEDVGPTS
  HNRKKARWDTLEPLDTGLSLAEDEELVLHLLRSQS
• Function: Putative ATP-dependent RNA helicase.
• Tissue Specificity: High in testis but widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Altered Expression	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[2]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[5]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[6]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Limited	Altered Expression	[4]

13 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 Probable ATP-dependent RNA helicase DDX10 (DDX10).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[18]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Probable ATP-dependent RNA helicase DDX10 (DDX10).	[20]

References

• [1] NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogntique Hmatologique.Leukemia. 2006 Apr;20(4):696-706. doi: 10.1038/sj.leu.2404130.
• [2] DDX10 overexpression predicts worse prognosis in osteosarcoma and its deletion prohibits cell activities modulated by MAPK pathway.Biochem Biophys Res Commun. 2019 Mar 19;510(4):525-529. doi: 10.1016/j.bbrc.2019.01.114. Epub 2019 Feb 6.
• [3] Recombinant PAPP-A resistant insulin-like growth factor binding protein 4 (dBP4) inhibits angiogenesis and metastasis in a murine model of breast cancer.BMC Cancer. 2018 Oct 22;18(1):1016. doi: 10.1186/s12885-018-4950-0.
• [4] Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia.Cancer Genet Cytogenet. 2005 Mar;157(2):104-8. doi: 10.1016/j.cancergencyto.2004.06.014.
• [5] Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-B pathway in ovarian cancer.Biochem Biophys Res Commun. 2016 Jan 22;469(4):1000-5. doi: 10.1016/j.bbrc.2015.12.069. Epub 2015 Dec 20.
• [6] Inv(11)(p15q22)/NUP98-DDX10 fusion and isoforms in a new case of de novo acute myeloid leukemia.Cancer Genet. 2013 Mar;206(3):92-6. doi: 10.1016/j.cancergen.2013.02.001. Epub 2013 Mar 20.
• [7] 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.
• [8] 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.
• [9] Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] 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.
• [12] 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.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] 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.
• [15] 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.
• [16] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [17] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [18] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [19] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [20] 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.