Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVJR3GL)

DOT Name Nicotinamide phosphoribosyltransferase (NAMPT)
Synonyms NAmPRTase; Nampt; EC 2.4.2.12; Pre-B-cell colony-enhancing factor 1; Pre-B cell-enhancing factor; Visfatin
Gene Name NAMPT
UniProt ID
NAMPT_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2E5B ; 2E5C ; 2E5D ; 2GVG ; 2GVJ ; 3DGR ; 3DHD ; 3DHF ; 3DKJ ; 3DKL ; 4JNM ; 4JR5 ; 4KFN ; 4KFO ; 4KFP ; 4L4L ; 4L4M ; 4LTS ; 4LV9 ; 4LVA ; 4LVB ; 4LVD ; 4LVF ; 4LVG ; 4LWW ; 4M6P ; 4M6Q ; 4N9B ; 4N9C ; 4N9D ; 4N9E ; 4O0Z ; 4O10 ; 4O12 ; 4O13 ; 4O14 ; 4O15 ; 4O16 ; 4O17 ; 4O18 ; 4O19 ; 4O1A ; 4O1B ; 4O1C ; 4O1D ; 4O28 ; 4WQ6 ; 5KIT ; 5LX3 ; 5LX5 ; 5NSD ; 5U2M ; 5U2N ; 5UPE ; 5UPF ; 5WI0 ; 5WI1 ; 6ATB ; 6AZJ ; 6B75 ; 6B76 ; 6E68 ; 6PEB ; 6TA0 ; 6TA2 ; 6TAC ; 7ENQ ; 7PPE ; 7PPF ; 7PPG ; 7PPH ; 7PPI ; 8DSC ; 8DSD ; 8DSE ; 8DSH ; 8DSI ; 8DSM ; 8DTJ ; 8F7L ; 8IVU
EC Number
2.4.2.12
Pfam ID
PF18127 ; PF04095
Sequence
MNPAAEAEFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKTENSKLRKVKYEETVFY
GLQYILNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEIKAVP
EGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSREQKKILAKYLLETS
GNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFKGTDTVAGLALIKKYYGTKDPVPGY
SVPAAEHSTITAWGKDHEKDAFEHIVTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIV
SRSTQAPLIIRPDSGNPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINT
LQEIVEGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKDPVAD
PNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGKVTKSYSFDEIRKNA
QLNIELEAAHH
Function
Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression.
Tissue Specificity Expressed in large amounts in bone marrow, liver tissue, and muscle. Also present in heart, placenta, lung, and kidney tissues.
KEGG Pathway
Nicoti.te and nicoti.mide metabolism (hsa00760 )
Metabolic pathways (hsa01100 )
NOD-like receptor sig.ling pathway (hsa04621 )
Reactome Pathway
Nicotinamide salvaging (R-HSA-197264 )
NPAS4 regulates expression of target genes (R-HSA-9768919 )
BMAL1 (R-HSA-1368108 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Methotrexate DM2TEOL Approved Nicotinamide phosphoribosyltransferase (NAMPT) affects the response to substance of Methotrexate. [39]
Mitoxantrone DMM39BF Approved Nicotinamide phosphoribosyltransferase (NAMPT) affects the response to substance of Mitoxantrone. [40]
------------------------------------------------------------------------------------
This DOT Affected the Biotransformations of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Nicotinamide-Adenine-Dinucleotide DM9LRKB Investigative Nicotinamide phosphoribosyltransferase (NAMPT) increases the chemical synthesis of Nicotinamide-Adenine-Dinucleotide. [41]
------------------------------------------------------------------------------------
43 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 Nicotinamide phosphoribosyltransferase (NAMPT). [1]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [6]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [12]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [14]
Marinol DM70IK5 Approved Marinol increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [15]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [16]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [17]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [18]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [19]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [20]
Rosiglitazone DMILWZR Approved Rosiglitazone affects the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [21]
Cidofovir DMA13GD Approved Cidofovir increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [22]
Ibuprofen DM8VCBE Approved Ibuprofen increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [22]
Nicotinamide DMUPE07 Approved Nicotinamide decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [23]
Berberine DMC5Q8X Phase 4 Berberine decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [23]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [24]
Coprexa DMA0WEK Phase 3 Coprexa increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [25]
DNCB DMDTVYC Phase 2 DNCB increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [26]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [27]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [28]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [29]
Eugenol DM7US1H Patented Eugenol increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [26]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [30]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [31]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [32]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [33]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [34]
D-glucose DMMG2TO Investigative D-glucose decreases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [34]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [35]
Manganese DMKT129 Investigative Manganese increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [36]
Tributylstannanyl DMHN7CB Investigative Tributylstannanyl increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [37]
NSC-1771 DMNXDGQ Investigative NSC-1771 increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [37]
OXYRESVERATROL DMN7S4L Investigative OXYRESVERATROL increases the expression of Nicotinamide phosphoribosyltransferase (NAMPT). [38]
------------------------------------------------------------------------------------
⏷ Show the Full List of 43 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 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.
3 Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
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 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
7 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
8 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.
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 Inhibition of nicotinamide phosphoribosyltransferase and depletion of nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of oral squamous cell carcinoma. Toxicol Appl Pharmacol. 2017 Sep 15;331:54-61. doi: 10.1016/j.taap.2017.05.008. Epub 2017 May 10.
11 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
12 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.
13 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
14 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
15 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
16 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
17 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
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 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
20 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
21 Visfatin is expressed in human granulosa cells: regulation by metformin through AMPK/SIRT1 pathways and its role in steroidogenesis. Mol Hum Reprod. 2013 May;19(5):313-26. doi: 10.1093/molehr/gat002. Epub 2013 Jan 11.
22 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
23 Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells. Toxicol Appl Pharmacol. 2016 Jan 15;291:70-83. doi: 10.1016/j.taap.2015.12.006. Epub 2015 Dec 19.
24 Resveratrol differentially regulates NAMPT and SIRT1 in Hepatocarcinoma cells and primary human hepatocytes. PLoS One. 2014 Mar 6;9(3):e91045. doi: 10.1371/journal.pone.0091045. eCollection 2014.
25 Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
26 Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
27 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
28 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
29 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.
30 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
31 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.
32 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
33 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
34 Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms. Diabetes. 2010 Apr;59(4):1006-15. doi: 10.2337/db09-1187. Epub 2010 Jan 12.
35 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
36 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.
37 THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers. Toxicol Appl Pharmacol. 2009 Apr 15;236(2):221-30.
38 Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells. Food Chem Toxicol. 2018 Aug;118:880-888.
39 Nicotinamide Phosphoribosyltransferase Attenuates Methotrexate Response in Juvenile Idiopathic Arthritis and In Vitro. Clin Transl Sci. 2016 Jun;9(3):149-57. doi: 10.1111/cts.12399. Epub 2016 May 11.
40 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.
41 Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase. Toxicol Sci. 2015 Mar;144(1):163-72. doi: 10.1093/toxsci/kfu268. Epub 2014 Dec 11.