63
Views
1
CrossRef citations to date
0
Altmetric
Review

Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) in cancer: a patent review

, , , &
Pages 565-582 | Received 13 Mar 2024, Accepted 07 Jun 2024, Published online: 13 Jun 2024

References

  • Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23(1):27–47. doi: 10.1016/j.cmet.2015.12.006
  • Houtkooper RH, Cantó C, Wanders RJ, et al. The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev. 2010 Apr;31(2):194–223. doi: 10.1210/er.2009-0026
  • Dölle C, Skoge RH, Vanlinden MR, et al. NAD biosynthesis in humans–enzymes, metabolites and therapeutic aspects. Curr Top Med Chem. 2013;13(23):2907–2917. doi: 10.2174/15680266113136660206
  • Ruggieri S, Orsomando G, Sorci L, et al. Regulation of NAD biosynthetic enzymes modulates NAD-sensing processes to shape mammalian cell physiology under varying biological cues. Biochim Biophys Acta. 2015;1854(9):1138–1149. doi: 10.1016/j.bbapap.2015.02.021
  • Chiarugi A, Dölle C, Felici R, et al. The NAD metabolome — a key determinant of cancer cell biology. Nat Rev Cancer. 2012;12(11):741–752. doi: 10.1038/nrc3340
  • Audrito V, Messana VG, Brandimarte L, et al. The extracellular NADome modulates immune responses. Front Immunol. 2021;12:704779. doi: 10.3389/fimmu.2021.704779
  • Zamporlini F, Ruggieri S, Mazzola F, et al. Novel assay for simultaneous measurement of pyridine mononucleotides synthesizing activities allows dissection of the NAD + biosynthetic machinery in mammalian cells. FEBS J. 2014;281(22):5104–5119. doi: 10.1111/febs.13050
  • Garten A, Schuster S, Penke M, et al. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol. 2015;11(9):535–546. doi: 10.1038/nrendo.2015.117
  • Heske CM. Beyond energy metabolism: exploiting the additional roles of NAMPT for Cancer Therapy. Front Oncol. 2020;9:1514. doi: 10.3389/fonc.2019.01514
  • Audrito V, Messana VG, Deaglio S. NAMPT and NAPRT: two metabolic enzymes with key roles in inflammation. Front Oncol. 2020;10:358. doi: 10.3389/fonc.2020.00358
  • Audrito V, Managò A, Gaudino F, et al. Targeting metabolic reprogramming in metastatic melanoma: the key role of nicotinamide phosphoribosyltransferase (NAMPT). Semin Cell Dev Biol. 2020;98:192–201. doi: 10.1016/j.semcdb.2019.05.001
  • Kitani T, Okuno S, Fujisawa H. Growth phase-dependent changes in the subcellular localization of pre-B-cell colony-enhancing factor 1. FEBS Lett. 2003;544(1–3):74–78. doi: 10.1016/S0014-5793(03)00476-9
  • Pittelli M, Formentini L, Faraco G, et al. Inhibition of nicotinamide phosphoribosyltransferase: cellular bioenergetics reveals a mitochondrial insensitive NAD pool. J Biol Chem. 2010;285(44):34106–34114. doi: 10.1074/jbc.M110.136739
  • Svoboda P, Krizova E, Sestakova S, et al. Nuclear transport of nicotinamide phosphoribosyltransferase is cell cycle–dependent in mammalian cells, and its inhibition slows cell growth. J Biol Chem. 2019;294(22):8676–8689. doi: 10.1074/jbc.RA118.003505
  • Zhu Y, Liu J, Park J, et al. Subcellular compartmentalization of NAD+ and its role in cancer: a sereNade of metabolic melodies. Pharmacol Ther. 2019;200:27–41. doi: 10.1016/j.pharmthera.2019.04.002
  • Takahashi R, Nakamura S, Nakazawa T, et al. Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. J Biochem. 2010;147(1):95–107. doi: 10.1093/jb/mvp152
  • Khan JA, Tao X, Tong L. Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. Nat Struct Mol Biol. 2006;13(7):582–588. doi: 10.1038/nsmb1105
  • Revollo JR, Körner A, Mills KF, et al. Nampt/PBEF/Visfatin regulates insulin secretion in β cells as a systemic NAD Biosynthetic Enzyme. Cell Metab. 2007;6(5):363–375. doi: 10.1016/j.cmet.2007.09.003
  • van den Bergh R, Morin S, Sass HJ, et al. Monocytes contribute to differential immune pressure on R5 versus X4 HIV through the adipocytokine visfatin/NAMPT. PLoS One. 2012;7(4):e35074. doi: 10.1371/journal.pone.0035074
  • Torretta S, Colombo G, Travelli C, et al. The cytokine nicotinamide phosphoribosyltransferase (eNAMPT; PBEF; Visfatin) Acts as a Natural Antagonist of C-C Chemokine Receptor Type 5 (CCR5). Cells. 2020;9(2):496. doi: 10.3390/cells9020496
  • Ratnayake D, Nguyen PD, Rossello FJ, et al. Macrophages provide a transient muscle stem cell niche via NAMPT secretion. Nature. 2021;591(7849):281–287. doi: 10.1038/s41586-021-03199-7
  • Camp SM, Ceco E, Evenoski CL, et al. Unique toll-like receptor 4 activation by NAMPT/PBEF induces NFκB signaling and inflammatory lung injury. Sci Rep. 2015;5(1):13135. doi: 10.1038/srep13135
  • Carbone F, Liberale L, Bonaventura A, et al. Regulation and function of extracellular nicotinamide phosphoribosyltransferase/Visfatin. Compr Physiol. 2017;7:603–621.
  • Managò A, Audrito V, Mazzola F, et al. Extracellular nicotinate phosphoribosyltransferase binds toll like receptor 4 and mediates inflammation. Nat Commun. 2019;10(1):4116. doi: 10.1038/s41467-019-12055-2
  • Romacho T, Valencia I, Ramos-González M, et al. Visfatin/eNampt induces endothelial dysfunction in vivo: a role for toll-like receptor 4 and NLRP3 inflammasome. Sci Rep. 2020;10(1):5386. doi: 10.1038/s41598-020-62190-w
  • Gasparrini M, Mazzola F, Cuccioloni M, et al. Molecular insights into the interaction between human nicotinamide phosphoribosyltransferase and toll-like receptor 4. J Biol Chem. 2022;298(3):101669. doi: 10.1016/j.jbc.2022.101669
  • Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? [published correction appears in Trends Biochem Sci. 2016 Mar;41(3): 287] [published correction appears in Trends Biochem Sci. 2016 Mar;41(3): 287]. Trends Biochem Sci. 2016;41(3):211–218. doi: 10.1016/j.tibs.2015.12.001
  • Chowdhry S, Zanca C, Rajkumar U, et al. NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling. Nature. 2019;569:570–575. doi: 10.1038/s41586-019-1150-2.
  • Dalamaga M, Christodoulatos GS, Mantzoros CS. The role of extracellular and intracellular Nicotinamide phosphoribosyl-transferase in cancer: Diagnostic and therapeutic perspectives and challenges. Metabolism. 2018;82:72–87. doi: 10.1016/j.metabol.2018.01.001
  • Yaku K, Okabe K, Hikosaka K, et al. NAD metabolism in cancer therapeutics. Front Oncol. 2018;8:622. doi: 10.3389/fonc.2018.00622
  • Tan B, Dong S, Shepard RL, et al. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT), an Enzyme Essential for NAD+ biosynthesis, leads to altered carbohydrate metabolism in cancer cells. J Biol Chem. 2015;290(25):15812–15824. doi: 10.1074/jbc.M114.632141
  • Audrito V, Managò A, La Vecchia S, et al. Nicotinamide Phosphoribosyltransferase (NAMPT) as a Therapeutic Target in BRAF-Mutated Metastatic Melanoma. J Natl Cancer Inst. 2018;110(3):290–303. doi: 10.1093/jnci/djx198
  • Kennedy BE, Sharif T, Martell E, et al. NAD+ salvage pathway in cancer metabolism and therapy. Pharmacol Res. 2016;114:274–283. doi: 10.1016/j.phrs.2016.10.027
  • Yong J, Cai S, Zeng Z. Targeting NAD+ metabolism: dual roles in cancer treatment. Front Immunol. 2023;14:1269896. doi: 10.3389/fimmu.2023.1269896
  • Audrito V, Managò A, Gaudino F, et al. NAD-Biosynthetic and consuming enzymes as central players of metabolic regulation of innate and adaptive Immune Responses in Cancer. Front Immunol. 2019;10:1720. doi: 10.3389/fimmu.2019.01720
  • Lucena-Cacace A, Otero-Albiol D, Jiménez-García MP, et al. NAMPT is a potent oncogene in colon cancer progression that modulates cancer stem cell properties and resistance to therapy through Sirt1 and PARP. Clin Cancer Res. 2018;24(5):1202–1215. doi: 10.1158/1078-0432.CCR-17-2575
  • Silveira SC, Buhagiar-Labarchède G, Onclercq-Delic R, et al. A decrease in NAMPT activity impairs basal PARP-1 activity in cytidine deaminase deficient-cells, independently of NAD. Sci Rep. 2020;10(1):13907. doi: 10.1038/s41598-020-70874-6
  • Zhao E, Hou J, Ke X, et al. The roles of sirtuin family proteins in cancer progression. Cancers (Basel). 2019;11(12):1949. doi: 10.3390/cancers11121949
  • Zhang B, Shi D, Zhang X, et al. FK866 inhibits the epithelial-mesenchymal transition of hepatocarcinoma MHCC97-H cells. Oncol Lett. 2018;16:7231–7238. doi: 10.3892/ol.2018.9541
  • Kim SR, Bae YH, Bae SK, et al. Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-κB activation in endothelial cells. Biochim Biophys Acta. 2008;1783(5):886–895. doi: 10.1016/j.bbamcr.2008.01.004
  • Soncini D, Caffa I, Zoppoli G, et al. Nicotinamide phosphoribosyltransferase promotes epithelial-to-mesenchymal transition as a soluble factor independent of its enzymatic activity. J Biol Chem. 2014;289(49):34189–34204. doi: 10.1074/jbc.M114.594721
  • Kim JY, Bae YH, Bae MK, et al. Visfatin through STAT3 activation enhances IL-6 expression that promotes endothelial angiogenesis. Biochim Biophys Acta. 2009;1793(11):1759–1767. doi: 10.1016/j.bbamcr.2009.09.006
  • Sica A, Strauss L, Consonni FM, et al. Metabolic regulation of suppressive myeloid cells in cancer. Cytokine Growth Factor Rev. 2017;35:27–35. doi: 10.1016/j.cytogfr.2017.05.002
  • Dutta T, Kapoor N, Mathew M, et al. Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans. Cell Rep. 2023;42(3):112218. doi: 10.1016/j.celrep.2023.112218
  • Murphy JP, Giacomantonio MA, Paulo JA, et al. The NAD+ salvage pathway supports PHGDH-Driven serine biosynthesis. Cell Rep. 2018;24(9):2381–2391.e5. doi: 10.1016/j.celrep.2018.07.086
  • Touat M, Sourisseau T, Dorvault N, et al. DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade. J Clin Invest. 2018;128(4):1671–1687. doi: 10.1172/JCI90277
  • Wang W, Yang C, Wang T, et al. Complex roles of nicotinamide N-methyltransferase in cancer progression. Cell Death Dis. 2022;13(3):267. doi: 10.1038/s41419-022-04713-z
  • Ghanem MS, Monacelli F, Nencioni A. Advances in NAD-Lowering agents for cancer treatment. Nutrients. 2021;13(5):1665. doi: 10.3390/nu13051665
  • Cea M, Cagnetta A, Fulciniti M, et al. Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition. Blood. 2012;120(17):3519–3529. doi: 10.1182/blood-2012-03-416776
  • Kozako T, Aikawa A, Ohsugi T, et al. High expression of NAMPT in adult T-cell leukemia/lymphoma and anti-tumor activity of a NAMPT inhibitor. Eur J Pharmacol. 2019;865:172738. doi: 10.1016/j.ejphar.2019.172738
  • Gasparrini M, Audrito V. NAMPT: A critical driver and therapeutic target for cancer. Int J Biochem Cell Biol. 2022;145:106189. doi: 10.1016/j.biocel.2022.106189
  • Quijada H, Bermudez T, Kempf CL, et al. Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody. Eur Respir J. 2021;57(5):2002536. doi: 10.1183/13993003.02536-2020
  • Colombo G, Clemente N, Zito A, et al. Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis. J Mol Med (Berl). 2020;98(4):595–612. doi: 10.1007/s00109-020-01892-0
  • Garcia AN, Casanova NG, Kempf CL, et al. eNAMPT is a novel damage-associated molecular pattern protein that contributes to the severity of radiation-induced lung fibrosis. Am J Respir Cell Mol Biol. 2022;66(5):497–509. doi: 10.1165/rcmb.2021-0357OC
  • Forma Tm, Llc. Novel compounds and compositions for the inhibition of nampt. WO2012150952A1. 2012.
  • Forma Therapeutics, Inc. Guanidine compounds and compositions for the inhibition of nampt. WO2012031199A1. 2012.
  • Forma Therapeutics, Inc. Genentech, Inc. 4- {[(pyridin- 3 - yl -methyl) aminocarbonyl] amino} benzene - sulfone derivatives as nampt inhibitors for therapy of diseases such as cancer. WO2012031196A1. 2012.
  • Genentech Inc, Forma Therapeutics Inc, Valo Early Discovery Inc. Novel compounds and compositions for the inhibition of nampt. US20210244717A1. 2021.
  • Valo Health Inc. Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (nampt). US20230110003A1. 2023.
  • Abbott Laboratories. Nampt inhibitors. WO2012067963A1. 2012.
  • Abbvie Inc. Nampt inhibitors. US20160193209A1. 2016.
  • AbbVie Inc. Nampt inhibitors. US20170253562A1. 2017.
  • Abbott Laboratories. Nampt and rock inhibitors. US20120122842A1. 2012.
  • AbbVie Inc. Nampt inhibitors. US20130303508A1. 2013.
  • Abbvie Inc. Nampt inhibitors. WO2013170113A1. 2013.
  • AbbVie Inc. Nampt inhibitors. US20170065575A1. 2017.
  • Aurigene Discovery Technologies Limited. 4,5-dihydroisoxazole derivatives as nampt inhibitors. WO2014111871A1. 2014.
  • Aurigene Discovery Technologies Limited. 4,5-dihydroisoxazole derivatives as nampt inhibitors. WO2016012958A1. 2016.
  • Aurigene Discovery Technologies Limited. Fused heterocyclyl derivatives as nampt inhibitors. WO2014141035A3. 2015.
  • Zhang RY, Qin Y, Lv XQ, et al. A fluorometric assay for high-throughput screening targeting nicotinamide phosphoribosyltransferase. Anal Biochem. 2011;412(1):18–25. doi: 10.1016/j.ab.2010.12.035
  • The Curators of The University of Missouri. Small molecule inhibitors of nicotinamide phosphoribosyltransferase (nampt).WO2013082150A1. 2013.
  • Genzyme Corporation. Nampt inhibitors and methods. WO2015179759A1. 2015.
  • Eli Lilly And Company. Novel pyridyloxyacetyl tetrahydroisoquinoline compounds useful as nampt inhibitors. WO2015054060A1. 2015.
  • Sunflower Research Llc. Therapeutic and diagnostic methods. US20160367541A1. 2016.
  • Seattle Genetics, Inc. Targeted delivery of nicotinamide adenine dinucleotide salvage pathway inhibitors. WO2018075600A1. 2018.
  • University Of Pittsburgh. Methods and materials for inhibiting nicotinamide phosphoribosyltransferase activity. WO2022109285A1. 2022.
  • Arizona Board of Regents of University of Arizona. Compositions and methods for treating pulmonary fibrosis. US20200138799A1. 2020.
  • University Of California. Interferon signaling as a cancer biomarker. WO2021102420A1. 2021.
  • New York University NYU. Combination therapy for treatment of lkb1 deficient cancers. US20220062260A1. 2022.
  • Zhang Y, Meng Q, Sun Q, et al. LKB1 deficiency-induced metabolic reprogramming in tumorigenesis and non-neoplastic diseases. Mol Metab. 2021;44:101131. doi: 10.1016/j.molmet.2020.101131
  • Bayer Pharma Aktiengesellschaft. Dihydropyridazinones substituted with phenylureas. WO2018086703A1. 2018.
  • Bayer Aktiengesellschaft. Bayer Pharma Aktiengesellschaft. Antibody drug conjugates (adcs) with nampt inhibitors. WO2019149637A1. 2019.
  • Ontario Institute For Cancer Research (Oicr). Nicotinamide phosphoribosyltransferase (nampt) inhibitor-conjugates and uses thereof. 2022:p. WO2022011458A1.
  • Ontario Institute For Cancer Research (Oicr). Nicotinamide phosphoribosyltransferase (nampt) inhibitor-conjugates and uses thereof. 2022:p. US20220313832A1.
  • Università Degli Studi Del Piemonte Orientale “Amedeo Avogadro”. “inhibitors of nicotinamide phosphoribosyltransferase, compositions, products and uses thereof”. 2014:p. WO2014178001A1.
  • Università Degli Studi Di Genova. Centre Hospitalier Universitaire Vaudois (Chuv). Sensitization of cancer cells to nampt inhibitors by nicotinic acid phosphoribosyltransferase neutralization. 2017:p. WO2017162840A1.
  • Millennium Pharmaceuticals, Inc. Quinoxaline compounds and uses thereof. WO2015161142A1. 2015.
  • Millennium Pharmaceuticals, Inc. Quinoxaline compounds and uses thereof. WO2016118565A1. 2016.
  • Mor Research Applications Ltd. Methods for prognosis and treatment of solid tumors. US20210180138A1. 2021.
  • Institut National de la Sante et de la Recherche Medicale INSERM, Universite Cote dAzur. Methods and compositions for treating melanoma resistant. 2021:p. US20210072244A1.
  • Apion Japan KK. Novel nampt inhibitor and an antitumor agent containing the same, screening method for novel nampt inhibitor, novel naprt inhibitor and antitumor agent containing the same, screening method for novel naprt inhibitor, method for increasing ratio of normal cells to tumor cells, and method to assist in prescribing antitumor agents. JP2019137638A. 2019.
  • Opko Curna Llc. Treatment of nicotinamide phosphoribosyltransferase (nampt) related diseases by inhibition of natural antisense transcript to nampt. 2012:p. WO2012024478A2.
  • Tian Lizhi. A kind of sulfamide derivative, preparation method and its it is antitumor in application. CN107903246A. 2018.
  • Tian Lizhi. A kind of sulfamide derivative, preparation method and its application as NAMPT inhibitor in antitumor drug. CN107954988A. 2018.
  • Tian Lizhi. A kind of sulfamide derivative and its application in antitumor drug. CN107954987A. 2018.
  • Tian Lizhi. A kind of sulfamide derivative and its application as NAMPT inhibitor. CN108042538A. 2018.
  • Second Military Medical University SMMU. A kind of Nampt nitrogen mustards inhibitor of multiple target point anti-tumor activity and its preparation and application. CN109776494A. 2019.
  • Second Military Medical University SMMU. NAMPT protein degradation targeting chimera and preparation method and application thereof. CN111454327A. 2020.
  • Second Military Medical University SMMU. Compound and application thereof in preparation of NAMPT protein autophagy degradation agent. CN114890990A. 2022.
  • Juyuan Shanghai Biotechnology Co ltd. NAMPT/HDAC double-target inhibitor and preparation method thereof. CN106916101A. 2017.
  • China Pharmaceutical University. A kind of novel NAMPT and IDO double inhibitors and preparation method thereof and medical usage. CN108530444A. 2018.
  • China Pharmaceutical University. A kind of benzo-aza virtue cyclics and its preparation method and application. CN107674059A. 2018.
  • Tianjin University of Science and Technology. Novel method for inhibiting activity of colon cancer cells by combining inhibitor and small interfering RNA. CN112156105A. 2021.
  • East China Normal University. Nicotinamide phosphoribosyl transferase inhibitors with tumor targeting. CN113896721A. 2022.
  • East China University of Science and Technology, Second Military Medical University SMMU. Compound serving as NAMPT-PDE delta double-target inhibitor and application thereof. CN116589402A. 2023.
  • Gasparrini M, Sorci L, Raffaelli N. Enzymology of extracellular NAD metabolism. Cell Mol Life Sci. 2021;78(7):3317–3331. doi: 10.1007/s00018-020-03742-1
  • Galli U, Colombo G, Travelli C, et al. Recent Advances in NAMPT Inhibitors: A Novel Immunotherapic Strategy. Front Pharmacol. 2020;11:656. doi: 10.3389/fphar.2020.00656
  • Semerena E, Nencioni A, Masternak K. Extracellular nicotinamide phosphoribosyltransferase: role in disease pathophysiology and as a biomarker. Front Immunol. 2023;14:1268756. doi: 10.3389/fimmu.2023.1268756
  • Piacente F, Caffa I, Ravera S, et al. Nicotinic acid phosphoribosyltransferase regulates cancer cell metabolism, susceptibility to NAMPT Inhibitors, and DNA repair. Cancer Res. 2017;77(14):3857–3869. doi: 10.1158/0008-5472.CAN-16-3079
  • Antolin AA, Workman P, Mestres J, et al. Polypharmacology in Precision Oncology: Current Applications and Future Prospects. Curr Pharm Des. 2016;22(46):6935–6945. doi: 10.2174/1381612822666160923115828
  • Amelio I, Lisitsa A, Knight RA, et al. Polypharmacology of approved anticancer drugs. Curr Drug Targets. 2017;18(5):534–543. doi: 10.2174/1389450117666160301095233
  • Békés M, Langley DR, Crews CM. PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug Discov. 2022;21(3):181–200. doi: 10.1038/s41573-021-00371-6
  • Wu Y, Pu C, Fu Y, et al. NAMPT-targeting PROTAC promotes antitumor immunity via suppressing myeloid-derived suppressor cell expansion. Acta Pharm Sin B. 2022;12(6):2859–2868. doi: 10.1016/j.apsb.2021.12.017
  • Zhu X, Liu H, Chen L, et al. Addressing the enzyme-independent tumor-promoting function of NAMPT via PROTAC-mediated degradation. Cell Chem Biol. 2022;29(11):1616–1629.e12. doi: 10.1016/j.chembiol.2022.10.007

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.