Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTGG2PM)

DOT Name DNA damage-induced apoptosis suppressor protein (DDIAS)
Synonyms Nitric oxide-inducible gene protein
Gene Name DDIAS
Related Disease
Advanced cancer ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Breast cancer ( )
Breast carcinoma ( )
Lung neoplasm ( )
Non-small-cell lung cancer ( )
UniProt ID
DDIAS_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF08646
Sequence
MNRRRKFLLASVLALQNSSFIYPSCQKCFSRIILVSKRSNCPKCGSTGESGNANYRYKLS
LKVAESNKLFVITVFGSCLDTFFGLTATGLHRYIQDPNKIPETLDNDTTQNLLTKAVETC
FVGQSFIFGVTNFENQPGQGSDASNFLQQCSDHKRKAKALVACQIVLPDPGIAGFTVIDY
FHQLLQTFNFRKLQCDSQAPNNHLLALDHSNSDLSSIYTSDSTSDFFKSCSKDTFSKFWQ
PSLEFTCIVSQLTDNDDFSASEQSKAFGTLQQNRKSISIAEATGSSSCHDPIQDSWSLVS
YMDKKSTAEKLGKELGLQAKELSAVHSSHHEIGVNDSNLFSLEMREPLESSNTKSFHSAV
EIKNRSQHELPCFQHHGIDTPTSLQKRSACCPPSLLRLEETASSSQDGDPQIWDDLPFSE
SLNKFLAVLESEIAVTQADVSSRKHHVDNDIDKFHADHSRLSVTPQRTTGALHTPPIALR
SSQVIVKANCSKDDFLFNCKGNLSPSVEKESQPDNKVEAVSVNHNGRDMSEYFLPNPYLS
ALSSSSKDLETIVTLKKTIRISPHRESDHSSLNNKYLNGCGEISVSEMNEKLTTLCYRKY
NDVSDLCKLENKQYCRWSKNQDDSFTICRKLTYPLETLCNSPNRSTNTLKEMPWGHINNN
VTQSYSIGYEGSYDASADLFDDIAKEMDIATEITKKSQDILLKWGTSLAESHPSESDFSL
RSLSEDFIQPSQKLSLQSLSDSRHSRTCSPTPHFQSDSEYNFENSQDFVPCSQSTPISGF
HQTRIHGINRAFKKPVFYSDLDGNYEKIRIFPENDKQQASPSCPKNIKTPSQKIRSPIVS
GVSQPDVFNHYPFAECHETDSDEWVPPTTQKIFPSDMLGFQGIGLGKCLAAYHFPDQQEL
PRKKLKHIRQGTNKGLIKKKLKNMLAAVVTKKKTHKYNCKSSGWISKCPDIQVLAAPQLH
PILGPDSCSEVKCCLPFSEKGPPSVCETRSAWSPELFS
Function May be an anti-apoptotic protein involved in DNA repair or cell survival.
Tissue Specificity Highly expressed in colorectal and lung cancer tissues.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Posttranslational Modification [1]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [1]
Lung cancer DISCM4YA Strong Biomarker [1]
Lung carcinoma DISTR26C Strong Biomarker [1]
Breast cancer DIS7DPX1 moderate Biomarker [2]
Breast carcinoma DIS2UE88 moderate Biomarker [2]
Lung neoplasm DISVARNB Limited Altered Expression [3]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [1]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 DNA damage-induced apoptosis suppressor protein (DDIAS). [4]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of DNA damage-induced apoptosis suppressor protein (DDIAS). [20]
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18 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [8]
Quercetin DM3NC4M Approved Quercetin increases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [9]
Temozolomide DMKECZD Approved Temozolomide increases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [11]
Testosterone DM7HUNW Approved Testosterone decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [11]
Triclosan DMZUR4N Approved Triclosan decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [12]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [13]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [14]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [16]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [17]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [18]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [19]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [8]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of DNA damage-induced apoptosis suppressor protein (DDIAS). [21]
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⏷ Show the Full List of 18 Drug(s)

References

1 DDIAS suppresses TRAIL-mediated apoptosis by inhibiting DISC formation and destabilizing caspase-8 in cancer cells.Oncogene. 2018 Mar;37(9):1251-1262. doi: 10.1038/s41388-017-0025-y. Epub 2017 Dec 15.
2 Simvastatin downregulates HER2 via upregulation of PEA3 to induce cell death in HER2-positive breast cancer cells.Oncol Res. 2012;20(5-6):187-95. doi: 10.3727/096504013x13589503482699.
3 DNA damage-induced apoptosis suppressor (DDIAS), a novel target of NFATc1, is associated with cisplatin resistance in lung cancer.Biochim Biophys Acta. 2016 Jan;1863(1):40-9. doi: 10.1016/j.bbamcr.2015.10.011. Epub 2015 Oct 25.
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 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
8 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
9 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.
10 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.
11 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
12 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
13 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.
14 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
15 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
16 Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands. Toxicol Lett. 2011 Oct 10;206(2):178-88.
17 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
18 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.
19 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
20 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
21 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.