Details of Drug Off-Target (DOT)

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

• DOT Name: GMP reductase 1 (GMPR)
• Synonyms: GMPR 1; EC 1.7.1.7; Guanosine 5'-monophosphate oxidoreductase 1; Guanosine monophosphate reductase 1
• Gene Name: GMPR
• Related Disease:
  Alzheimer disease
  Juvenile idiopathic arthritis
  Major depressive disorder
  Melanoma
• UniProt ID: GMPR1_HUMAN
• PDB ID: 2BLE; 2BWG
• EC Number: 1.7.1.7
• Pfam ID: PF00478
• Sequence:
  MPRIDADLKLDFKDVLLRPKRSSLKSRAEVDLERTFTFRNSKQTYSGIPIIVANMDTVGT
  FEMAAVMSQHSMFTAIHKHYSLDDWKLFATNHPECLQNVAVSSGSGQNDLEKMTSILEAV
  PQVKFICLDVANGYSEHFVEFVKLVRAKFPEHTIMAGNVVTGEMVEELILSGADIIKVGV
  GPGSVCTTRTKTGVGYPQLSAVIECADSAHGLKGHIISDGGCTCPGDVAKAFGAGADFVM
  LGGMFSGHTECAGEVFERNGRKLKLFYGMSSDTAMNKHAGGVAEYRASEGKTVEVPYKGD
  VENTILDILGGLRSTCTYVGAAKLKELSRRATFIRVTQQHNTVFS
• Function: Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway: Purine salvage (R-HSA-74217)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Posttranslational Modification	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[2]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[3]
Melanoma	DIS1RRCY	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	GMP reductase 1 (GMPR) affects the response to substance of Acetaminophen.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of GMP reductase 1 (GMPR).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of GMP reductase 1 (GMPR).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of GMP reductase 1 (GMPR).	[14]

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 GMP reductase 1 (GMPR).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GMP reductase 1 (GMPR).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of GMP reductase 1 (GMPR).	[9]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of GMP reductase 1 (GMPR).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of GMP reductase 1 (GMPR).	[11]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of GMP reductase 1 (GMPR).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of GMP reductase 1 (GMPR).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of GMP reductase 1 (GMPR).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of GMP reductase 1 (GMPR).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of GMP reductase 1 (GMPR).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GMP reductase 1 (GMPR).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of GMP reductase 1 (GMPR).	[18]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of GMP reductase 1 (GMPR).	[19]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of GMP reductase 1 (GMPR).	[20]

References

• [1] Guanosine monophosphate reductase 1 is a potential therapeutic target for Alzheimer's disease.Sci Rep. 2018 Feb 9;8(1):2759. doi: 10.1038/s41598-018-21256-6.
• [2] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [3] Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.Am J Psychiatry. 2013 Feb;170(2):207-17. doi: 10.1176/appi.ajp.2012.12020237.
• [4] Microphthalmia-associated transcription factor suppresses invasion by reducing intracellular GTP pools.Oncogene. 2017 Jan 5;36(1):84-96. doi: 10.1038/onc.2016.178. Epub 2016 May 16.
• [5] 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.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] 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.
• [10] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [11] Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect. 2015 Jan;123(1):80-7. doi: 10.1289/ehp.1408437. Epub 2014 Aug 19.
• [12] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] 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.
• [15] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] 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] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [19] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [20] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [21] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.