Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8SMO3N)

• DOT Name: Deoxyribose-phosphate aldolase (DERA)
• Synonyms: DERA; EC 4.1.2.4; 2-deoxy-D-ribose 5-phosphate aldolase; Phosphodeoxyriboaldolase; Deoxyriboaldolase
• Gene Name: DERA
• Related Disease:
  Breast carcinoma
  Cutaneous melanoma
  Glaucoma/ocular hypertension
  Melanoma
• UniProt ID: DEOC_HUMAN
• EC Number: 4.1.2.4
• Pfam ID: PF01791
• Sequence:
  MSAHNRGTELDLSWISKIQVNHPAVLRRAEQIQARRTVKKEWQAAWLLKAVTFIDLTTLS
  GDDTSSNIQRLCYKAKYPIREDLLKALNMHDKGITTAAVCVYPARVCDAVKALKAAGCNI
  PVASVAAGFPAGQTHLKTRLEEIRLAVEDGATEIDVVINRSLVLTGQWEALYDEIRQFRK
  ACGEAHLKTILATGELGTLTNVYKASMIAMMAGSDFIKTSTGKETVNATFPVAIVMLRAI
  RDFFWKTGNKIGFKPAGGIRSAKDSLAWLSLVKEELGDEWLKPELFRIGASTLLSDIERQ
  IYHHVTGRYAAYHDLPMS
• Function: Catalyzes a reversible aldol reaction between acetaldehyde and D-glyceraldehyde 3-phosphate to generate 2-deoxy-D-ribose 5-phosphate. Participates in stress granule (SG) assembly. May allow ATP production from extracellular deoxyinosine in conditions of energy deprivation.
• Tissue Specificity: Mainly expressed in liver, lung and colon.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Pentose phosphate pathway (R-HSA-71336)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Cutaneous melanoma	DIS3MMH9	Strong	Biomarker	[2]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Genetic Variation	[3]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Deoxyribose-phosphate aldolase (DERA) affects the response to substance of Vinblastine.	[20]

3 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 Deoxyribose-phosphate aldolase (DERA).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Deoxyribose-phosphate aldolase (DERA).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Deoxyribose-phosphate aldolase (DERA).	[18]

14 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 Deoxyribose-phosphate aldolase (DERA).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Deoxyribose-phosphate aldolase (DERA).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Deoxyribose-phosphate aldolase (DERA).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Deoxyribose-phosphate aldolase (DERA).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Deoxyribose-phosphate aldolase (DERA).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Deoxyribose-phosphate aldolase (DERA).	[8]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Deoxyribose-phosphate aldolase (DERA).	[19]

References

• [1] Genetic predictors of chemotherapy-related amenorrhea inwomen with breast cancer.Fertil Steril. 2019 Oct;112(4):731-739.e1. doi: 10.1016/j.fertnstert.2019.05.018. Epub 2019 Jul 29.
• [2] Establishment and characterization of a cell line (DEOC-1) originating from a human malignant melanoma of the skin.Hum Cell. 2007 May;20(2):23-38. doi: 10.1111/j.1749-0774.2007.00028.x.
• [3] Genome-wide association and admixture analysis of glaucoma in the Women's Health Initiative.Hum Mol Genet. 2014 Dec 15;23(24):6634-43. doi: 10.1093/hmg/ddu364. Epub 2014 Jul 15.
• [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] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] 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.
• [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] 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.
• [12] 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.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.
• [18] 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.
• [19] Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.