The Pharmacology of CD38/NADase: An Emerging Target in Cancer and Diseases of Aging

Trends in Pharmacological Sciences

Volumn 39, Issue 4, 2018, Pages 424-436

  Chini, Eduardo N ^a   Chini, Claudia C S ^a   Espindola Netto, Jair Machado ^a   de Oliveira, Guilherme C ^a   van Schooten, Wim ^b  

^a Mayo Clinic College of Medicine   (United States)

^b Teneobio Inc   (United States)

Author keywords

aging; antibodies; cancer and metabolism; CD38; NAD+; NADase; sirtuins; small molecules

Indexed keywords

ADENOSINE DIPHOSPHATE RIBOSE; ADP RIBOSYL CYCLASE/CYCLIC ADP RIBOSE HYDROLASE 1; ANTINEOPLASTIC AGENT; APIGENIN; CYANIDIN 3 GLUCOSIDE; DARATUMUMAB; ISATUXIMAB; LUTEOLINIDIN; MOR 202; NICOTINAMIDE ADENINE DINUCLEOTIDE NUCLEOSIDASE; RHEIN; SIRTUIN; TAK 079; UNCLASSIFIED DRUG; ANTIBODY; NICOTINAMIDE ADENINE DINUCLEOTIDE;

AGING; ASTHMA; BINDING AFFINITY; CALCIUM SIGNALING; CELLULAR DISTRIBUTION; DIABETES MELLITUS; DRUG DETERMINATION; DRUG STRUCTURE; ENZYME ACTIVITY; HEART DISEASE; HUMAN; INFLAMMATION; MALIGNANT NEOPLASM; MULTIPLE MYELOMA; NONHUMAN; OBESITY; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN METABOLISM; PROTEIN TARGETING; REGULATORY MECHANISM; REVIEW; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; ENZYMOLOGY; IMMUNOLOGY; METABOLISM; MOLECULAR LIBRARY; MOLECULARLY TARGETED THERAPY; NEOPLASM; PHARMACOLOGY; PHYSIOLOGY;

ADP-RIBOSYL CYCLASE 1; AGING; ANIMALS; ANTIBODIES; HUMANS; MOLECULAR TARGETED THERAPY; NAD; NAD+ NUCLEOSIDASE; NEOPLASMS; SMALL MOLECULE LIBRARIES;

EID: 85042385950     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2018.02.001     Document Type: Review

References (83)

1. Chini, C.C.S., et al. NAD and the aging process: role in life, death and everything in between. Mol. Cell. Endocrinol. 455 (2017), 62–74.
2. + in aging, metabolism, and neurodegeneration. Science 350 (2015), 1208–1213.
3. + and sirtuins in aging and disease. Trends Cell Biol. 24 (2014), 464–471.
4. + declines during aging: it's destroyed. Cell Metab. 23 (2016), 965–966.
5. + induces a pseudohypoxic state disrupting nuclear–mitochondrial communication during aging. Cell 155 (2013), 1624–1638.
6. Camacho-Pereira, J., et al. CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab. 23 (2016), 1127–1139.
7. +/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154 (2013), 430–441.
8. + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14 (2011), 528–536.
9. de Picciotto, N.E., et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15 (2016), 522–530.
10. + repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352 (2016), 1436–1443.
11. North, B.J., et al. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J. 33 (2014), 1438–1453.
12. Mills, K.F., et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 24 (2016), 795–806.
13. + activate Sirt1 to rescue premature aging in Cockayne syndrome. Cell Metab. 20 (2014), 840–855.
14. Williams, P.A., et al. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science 355 (2017), 756–760.
15. Koenekoop, R.K., et al. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat. Genet. 44 (2012), 1035–1039.
16. Someya, S., et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143 (2010), 802–812.
17. + precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 20 (2014), 1059–1068.
18. + precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity. Cell Metab. 15 (2012), 838–847.
19. Barbosa, M.T., et al. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. FASEB J. 21 (2007), 3629–3639.
20. Trammell, S.A.J., et al. Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice. Sci. Rep., 6, 2016, 26933.
21. Gariani, K., et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology 63 (2016), 1190–1204.
22. + levels required for sirtuin's deacetylase activity. Exp. Mol. Pathol. 100 (2016), 303–306.
23. + synthesis by oncogenic URI causes liver tumorigenesis through DNA damage. Cancer Cell 26 (2014), 826–839.
24. + precursor, rescues age-associated susceptibility to AKI in a sirtuin 1-dependent manner. J. Am. Soc. Nephrol. 28 (2017), 2337–2352.
25. Tran, M.T., et al. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature 531 (2016), 528–532.
26. Boslett, J., et al. Endothelial cells highly express CD38 with activation by hypoxia/reoxygenation depleting NAD(P)H. Am. J. Physiol. Cell Physiol., 2017, 10.1152/ajpcell.00139.2017 Published online November 29, 2017.
27. + administration significantly protects against myocardial ischemia/reperfusion injury in rat model. Am. J. Transl. Res. 8 (2016), 3342–3350.
28. + destruction. Science 348 (2015), 453–457.
29. + degradation and dramatically ameliorates brain damage following global cerebral ischemia. Neurobiol. Dis. 95 (2016), 102–110.
30. + repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci. Transl. Med., 8, 2016, 361ra139.
31. +-Dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease. Cell Metab. 19 (2014), 1042–1049.
32. Shi, H., et al. NAD deficiency, congenital malformations, and niacin supplementation. N. Engl. J. Med. 377 (2017), 544–552.
33. Longo, V.D., et al. Interventions to slow aging in humans: are we ready?. Aging Cell 14 (2015), 497–510.
34. Aksoy, P., et al. Regulation of SIRT 1 mediated NAD dependent deacetylation: a novel role for the multifunctional enzyme CD38. Biochem. Biophys. Res. Commun. 349 (2006), 353–359.
35. Aksoy, P., et al. Regulation of intracellular levels of NAD: a novel role for CD38. Biochem. Biophys. Res. Commun. 345 (2006), 1386–1392.
36. Chiang, S.H., et al. Genetic ablation of CD38 protects against western diet-induced exercise intolerance and metabolic inflexibility. PLoS One, 10, 2015, e0134927.
37. Hu, Y., et al. Overexpression of CD38 decreases cellular NAD levels and alters the expression of proteins involved in energy metabolism and antioxidant defense. J. Proteome Res. 13 (2014), 786–795.
38. Malavasi, S., et al. Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol. Rev. 88 (2008), 841–886.
39. Chini, E.N., CD38 as a regulator of cellular NAD: a novel potential pharmacological target for metabolic conditions. Curr. Pharm. Des. 15 (2009), 57–63.
40. Deshpande, D.A., et al. CD38 in the pathogenesis of allergic airway disease: potential therapeutic targets. Pharmacol. Ther. 172 (2017), 116–126.
41. Lokhorst, H.M., et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N. Engl. J. Med. 373 (2015), 1207–1219.
42. van de Donk, N., et al. CD38 antibodies in multiple myeloma: back to the future. Blood 131 (2018), 13–29.
43. de Weers, M., et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J. Immunol. 186 (2011), 1840–1848.
44. +-metabolizing ectoenzymes in remodeling tumor–host interactions: the human myeloma model. Cells 4 (2015), 520–537.
45. Krejcik, J., et al. Monocytes and granulocytes reduce CD38 expression levels on myeloma cells in patients treated with daratumumab. Clin. Cancer Res. 23 (2017), 7498–7511.
46. Feng, X., et al. Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma. Clin. Cancer Res. 23 (2017), 4290–4300.
47. Nijhof, I.S., et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood 128 (2016), 959–970.
48. + hematologic malignancies. Clin. Cancer Res. 20 (2014), 4574–4583.
49. Martin, T., et al. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood 129 (2017), 3294–3303.
50. + axis regulates immunotherapeutic anti-tumor T cell response. Cell Metab. 27 (2018), 85–100.
51. + into a calcium-mobilizing metabolite. Cell. Regul. 3 (1991), 203–209.
52. Matalonga, J., et al. The nuclear receptor LXR limits bacterial infection of host macrophages through a mechanism that impacts cellular NAD metabolism. Cell Rep. 18 (2017), 1241–1255.
53. Franceschi, C., Campisi, J., Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69 (2014), S4–S9.
54. Shrimp, J.H., et al. Revealing CD38 cellular localization using a cell permeable, mechanism-based fluorescent small-molecule probe. J. Am. Chem. Soc. 136 (2014), 5656–5663.
55. + biosynthesis in FK866-treated tumor cells J. Biol. Chem. 288 (2013), 25938–25949.
56. Liu, J., et al. Cytosolic interaction of type III human CD38 with CIB1 modulates cellular cyclic ADP-ribose levels. Proc. Natl. Acad. Sci. 114 (2017), 8283–8288.
57. Zielinska, W., et al. Metabolism of cyclic ADPribose: zinc is an endogenous modulator of the cyclase/NAD glycohydrolase ratio of a CD38-like enzyme from human seminal fluid. Life Sci. 74 (2004), 1781–1790.
58. Sauve, A.A., A covalent intermediate in CD38 is responsible for ADP-ribosylation and cyclization reactions. J. Am. Chem. Soc. 122 (2000), 7855–7859.
59. Zhang, S., et al. Comparative analysis of pharmacophore features and quantitative structure–activity relationships for CD38 covalent and non-covalent inhibitors. Chem. Biol. Drug Des. 86 (2015), 1411–1424.
60. Liu, Q., et al. Structural basis for enzymatic evolution from a dedicated ADP-ribosyl cyclase to a multifunctional NAD hydrolase. J. Biol. Chem. 284 (2009), 27637–27645.
61. Horenstein, A.L., et al. Adenosine generated in the bone marrow niche through a CD38-mediated pathway correlates with progression of human myeloma. Mol. Med. 22 (2016), 694–704.
62. Krauset, D., et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature 508 (2014), 258–262.
63. + cosubstrate specificity of a Sir2 enzyme. Mol. Cell 17 (2005), 855–868.
64. + cell depletion with TAK-079 reduces arthritis in a cynomolgus collagen-induced arthritis (CIA) model. J. Immunol., 198(Suppl. 1), 2017 127.17.
65. 2+ signaling. Messenger 2 (2013), 19–32.
66. +. J. Biol. Chem. 267 (1992), 9606–9611.
67. Slama, J.T., Simmons, A.M., Carbanicotinamide adenine dinucleotide: synthesis and enzymological properties of a carbocyclic analogue of oxidized nicotinamide adenine dinucleotide. Biochemistry 27 (1988), 183–193.
68. + glycohydrolase activity of CD38 by carbocyclic NAD analogues. Biochem. J. 335 (1998), 631–636.
69. Sauve, A.A., Schramm, V.L., Mechanism-based inhibitors of CD38: a mammalian cyclic ADP-ribose synthetase. Biochemistry 41 (2002), 8455–8463.
70. Kwong, A.K.Y., et al. Catalysis-based Inhibitors of the calcium signaling function of CD38. Biochemistry 51 (2012), 555–564.
71. Kellenberger, E., et al. Flavonoids as inhibitors of human CD38. Bioorg. Med. Chem. Lett. 21 (2011), 3939–3942.
72. + metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes 62 (2013), 1084–1093.
73. Boslett, J., et al. Luteolinidin protects the postischemic heart through CD38 inhibition with preservation of NAD(P)(H). J. Pharmacol. Exp. Ther. 361 (2017), 99–108.
74. Shu, B., et al. Blockade of CD38 diminishes lipopolysaccharide-induced macrophage classical activation and acute kidney injury involving NF-κB signaling suppression. Cell. Signal. 42 (2018), 249–258.
75. Blacher, E., et al. Inhibition of glioma progression by a newly discovered CD38 inhibitor. Int. J. Cancer 136 (2015), 1422–1433.
76. Blacher, E., et al. Targeting CD38 in the tumor microenvironment; a novel approach to treat glioma. Cancer Cell Microenviron., 2, 2015, e486.
77. Schiavoni, I., et al. CD38 modulates respiratory syncytial virus-driven pro-inflammatory processes in human monocyte-derived dendritic cells. Immunology, 2017, 10.1111/imm.12873 Published online November 27, 2017.
78. Haffner, C.D., et al. Discovery, synthesis, and biological evaluation of thiazoloquin(az)olin(on)es as potent CD38 inhibitors. J. Med. Chem. 58 (2015), 3548–3571.
79. Becherer, J.D., et al. Discovery of 4-amino-8-quinoline carboxamides as novel, submicromolar inhibitors of NAD-hydrolyzing enzyme CD38. J. Med. Chem. 58 (2015), 7021–7056.
80. +. Science 352 (2016), 1474–1477.
81. +/NADH sensor, allows high-throughput metabolic screening of anti-tumor agents. Cell Metab. 21 (2015), 777–789.
82. Partida-Sanchez, D.A., et al. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat. Med. 7 (2001), 1209–1216.
83. Lopatina, O., et al. The roles of oxytocin and CD38 in social or parental behaviors. Front. Neurosci., 6, 2012, 182.