Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0STQLV)

• DOT Name: Nicotinamide riboside kinase 1 (NMRK1)
• Synonyms: NRK 1; NmR-K 1; EC 2.7.1.22; Nicotinic acid riboside kinase 1; EC 2.7.1.173; Ribosylnicotinamide kinase 1; RNK 1; Ribosylnicotinic acid kinase 1
• Gene Name: NMRK1
• Related Disease: Tourette syndrome
• UniProt ID: NRK1_HUMAN
• PDB ID: 2P0E; 2QG6; 2QL6; 2QSY; 2QSZ; 2QT0; 2QT1
• EC Number: 2.7.1.173; 2.7.1.22
• Pfam ID: PF13238
• Sequence:
  MKTFIIGISGVTNSGKTTLAKNLQKHLPNCSVISQDDFFKPESEIETDKNGFLQYDVLEA
  LNMEKMMSAISCWMESARHSVVSTDQESAEEIPILIIEGFLLFNYKPLDTIWNRSYFLTI
  PYEECKRRRSTRVYQPPDSPGYFDGHVWPMYLKYRQEMQDITWEVVYLDGTKSEEDLFLQ
  VYEDLIQELAKQKCLQVTA
• Function: Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). The enzyme also phosphorylates the antitumor drugs tiazofurin and 3-deazaguanosine.
• KEGG Pathway:
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Nicotinate metabolism (R-HSA-196807)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	No Known	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Nicotinamide riboside kinase 1 (NMRK1).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[8]
Estrone	DM5T6US	Approved	Estrone increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[8]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[14]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[15]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL increases the expression of Nicotinamide riboside kinase 1 (NMRK1).	[16]

References

• [1] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] 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.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [12] 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.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells. Food Chem Toxicol. 2018 Aug;118:880-888.