Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEZVTI1)

DOT Name	5-hydroxymethyl-dUMP N-hydrolase (DNPH1)
Synonyms	EC 3.2.2.-; 2'-deoxynucleoside 5'-phosphate N-hydrolase 1; c-Myc-responsive protein RCL
Gene Name	DNPH1
UniProt ID	DNPH1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	4P5E; 8OS9; 8OSC; 8QHQ; 8QHR
EC Number	3.2.2.-
Pfam ID	PF05014
Sequence	MAAAMVPGRSESWERGEPGRPALYFCGSIRGGREDRTLYERIVSRLRRFGTVLTEHVAAA ELGARGEEAAGGDRLIHEQDLEWLQQADVVVAEVTQPSLGVGYELGRAVAFNKRILCLFR PQSGRVLSAMIRGAADGSRFQVWDYEEGEVEALLDRYFEADPPGQVAASPDPTT
Function	Part of a nucleotide salvage pathway that eliminates epigenetically modified 5-hydroxymethyl-dCMP (hmdCMP) in a two-step process entailing deamination to cytotoxic 5-hydroxymethyl-dUMP (hmdUMP), followed by its hydrolysis into 5-hydroxymethyluracil (hmU) and 2-deoxy-D-ribose 5-phosphate (deoxyribosephosphate). Catalyzes the second step in that pathway, the hydrolysis of the N-glycosidic bond in hmdUMP, degrading this cytotoxic nucleotide to avoid its genomic integration.
Tissue Specificity	Expressed at low levels in brain, colon, lung, peripheral blood leukocytes, placenta, small intestine, and thymus. Expressed at high levels in heart, kidney, liver, skeletal muscle and spleen. Overexpressed in a significant proportion of breast cancers.
Reactome Pathway	Purine catabolism (R-HSA-74259 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[9]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[11]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[12]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[19]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[8]
Manganese	DMKT129	Investigative	Manganese decreases the expression of 5-hydroxymethyl-dUMP N-hydrolase (DNPH1).	[20]
------------------------------------------------------------------------------------


⏷ Show the Full List of 21 Drug(s)

References

1	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
3	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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	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.
8	Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
9	Analysis of gene expression induced by diethylstilbestrol (DES) in human primitive Mullerian duct cells using microarray. Cancer Lett. 2005 Apr 8;220(2):197-210.
10	The use of genomics technology to investigate gene expression changes in cultured human liver cells. Toxicol In Vitro. 2001 Aug-Oct;15(4-5):399-405. doi: 10.1016/s0887-2333(01)00043-1.
11	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
12	Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
13	Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
14	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15	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.
16	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.
17	Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
18	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
19	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
20	Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.