Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6SKKLL)

• DOT Name: Nicotinate-nucleotide pyrophosphorylase (QPRT)
• Synonyms: EC 2.4.2.19; Quinolinate phosphoribosyltransferase ; QAPRTase; QPRTase
• Gene Name: QPRT
• Related Disease:
  Hepatitis C virus infection
  Huntington disease
  Malignant glioma
  Acute myelogenous leukaemia
  Childhood kidney Wilms tumor
  Neuroblastoma
  Thyroid gland follicular carcinoma
  Wilms tumor
• UniProt ID: NADC_HUMAN
• PDB ID: 2JBM; 4KWV; 4KWW; 5AYX; 5AYY; 5AYZ
• EC Number: 2.4.2.19
• Pfam ID: PF01729 ; PF02749
• Sequence:
  MDAEGLALLLPPVTLAALVDSWLREDCPGLNYAALVSGAGPSQAALWAKSPGVLAGQPFF
  DAIFTQLNCQVSWFLPEGSKLVPVARVAEVRGPAHCLLLGERVALNTLARCSGIASAAAA
  AVEAARGAGWTGHVAGTRKTTPGFRLVEKYGLLVGGAASHRYDLGGLVMVKDNHVVAAGG
  VEKAVRAARQAADFTLKVEVECSSLQEAVQAAEAGADLVLLDNFKPEELHPTATVLKAQF
  PSVAVEASGGITLDNLPQFCGPHIDVISMGMLTQAAPALDFSLKLFAKEVAPVPKIH
• Function: Involved in the catabolism of quinolinic acid (QA).
• KEGG Pathway:
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Nicotinate metabolism (R-HSA-196807)
• BioCyc Pathway: MetaCyc:HS02508-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[1]
Huntington disease	DISQPLA4	Strong	Biomarker	[2]
Malignant glioma	DISFXKOV	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[4]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[4]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[5]
Thyroid gland follicular carcinoma	DISFK2QT	Limited	Biomarker	[6]
Wilms tumor	DISB6T16	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Nicotinate-nucleotide pyrophosphorylase (QPRT) decreases the response to substance of Arsenic.	[24]

17 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 Nicotinate-nucleotide pyrophosphorylase (QPRT).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[18]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[22]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL decreases the expression of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nicotinate-nucleotide pyrophosphorylase (QPRT).	[19]

References

• [1] Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection.Sci Rep. 2017 Jul 19;7(1):5876. doi: 10.1038/s41598-017-06254-4.
• [2] Basal ganglia lesions in the rat: effects on quinolinic acid metabolism.Brain Res. 1989 Jun 19;490(1):103-9. doi: 10.1016/0006-8993(89)90435-6.
• [3] Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis.Sci Rep. 2016 Jan 25;6:19681. doi: 10.1038/srep19681.
• [4] Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of Wilms' tumor gene 1 (WT1) protein in leukemic cells.Biochem Biophys Res Commun. 2017 Jan 22;482(4):802-807. doi: 10.1016/j.bbrc.2016.11.114. Epub 2016 Nov 23.
• [5] Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model.Mol Autism. 2018 Nov 6;9:56. doi: 10.1186/s13229-018-0239-z. eCollection 2018.
• [6] QPRT: a potential marker for follicular thyroid carcinoma including minimal invasive variant; a gene expression, RNA and immunohistochemical study.BMC Cancer. 2009 Mar 26;9:93. doi: 10.1186/1471-2407-9-93.
• [7] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [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] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [14] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [15] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] Proteomics analysis of human umbilical vein endothelial cells treated with resveratrol. Amino Acids. 2012 Oct;43(4):1671-8. doi: 10.1007/s00726-012-1248-4. Epub 2012 Feb 18.
• [19] 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.
• [20] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells. Food Chem Toxicol. 2018 Aug;118:880-888.
• [24] Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility. Toxicol Appl Pharmacol. 2008 Jan 15;226(2):199-205. doi: 10.1016/j.taap.2007.09.004. Epub 2007 Sep 15.