Discovery of a novel nicotinamide phosphoribosyl transferase (nampt) inhibitor via in silico screening

Biological and Pharmaceutical Bulletin

Volumn 37, Issue 1, 2014, Pages 31-36

  Takeuchi, Mikio ^a,b   Niimi, Tatsuya ^a   Masumoto, Mari ^a   Orita, Masaya ^a   Yokota, Hiroyuki ^a   Yamamoto, Tomoko ^b  

^a ASTELLAS PHARMA INC   (Japan)

^b CHIBA UNIVERSITY   (Japan)

Author keywords

FK866; In silico screening; Nicotinamide adenine dinucleotide; Nicotinamide phosphoribosyl transferase

Indexed keywords

AS 1604498; AS 2292427; AS 2334990; DAPORINAD; ENZYME INHIBITOR; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; RADIOISOTOPE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL ASSAY; CELL STRAIN K 562; COMPUTER MODEL; DRUG POTENCY; DRUG RESEARCH; DRUG SCREENING; DRUG STRUCTURE; DRUG TARGETING; ENZYME ASSAY; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IC 50; STRUCTURE ANALYSIS;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; COMPUTER SIMULATION; DRUG DISCOVERY; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; K562 CELLS; LEUKEMIA; MICE; NAD; NIACINAMIDE; NICOTINAMIDE MONONUCLEOTIDE; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE;

EID: 84892577816     PISSN: 09186158     EISSN: 13475215     Source Type: Journal    
DOI: 10.1248/bpb.b13-00495     Document Type: Article

References (20)

1. Belenky P, Bogan KL, Brenner C. NAD+ metabolism in health and disease. Trends Biochem. Sci., 32, 12-19 (2007)
2. Koch-Nolte F, Haag F, Guse AH, Lund F, Ziegler M. Emerging roles of NAD+ and its metabolites in cell signaling. Sci. Signal., 2, mr1 (2009)
3. Imai S. Dissecting systemic control of metabolism and aging in the NAD World: The importance of SIRT1 and NAMPT-mediated NAD biosynthesis. FEBS Lett., 585, 1657-1662 (2011).
4. Van Gool F, Galli M, Gueydan C, Kruys V, Prevot PP, Bedalov A, Mostoslavsky R, Alt FW, De Smedt T, Leo O. Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuindependent manner. Nat. Med., 15, 206-210 (2009)
5. Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C, Takahashi JS, Imai S, Bass J. Circadian clock feedback cycle through NAMPTmediated NAD+ biosynthesis. Science, 324, 651-654 (2009)
6. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P. Circadian control of the NAD+ salvage pathway by CLOCKSIRT1. Science, 324, 654-657 (2009)
7. Imai S. The NAD World: A new systemic regulatory network for metabolism and aging- Sirt1, systemic NAD biosynthesis, and their importance. Cell Biochem. Biophys., 53, 65-74 (2009)
8. Hasmann M, Schemainda I. FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res., 63, 7436-7442 (2003)
9. Bruzzone S, Fruscione F, Morando S, Ferrando T, Poggi A, Garuti A, D'Urso A, Selmo M, Benvenuto F, Cea M, Zoppoli G, Moran E, Soncini D, Ballestrero A, Sordat B, Patrone F, Mostoslavsky R, Uccelli A, Nencioni A. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE. PLoS ONE, 4, e7897 (2009)
10. Holen K, Saltz LB, Hollywood E, Burk K, Hanauske AR. The pharmacokinetics, toxicities, and biologic effects of FK866, a nicotinamide adenine dinucleotide biosynthesis inhibitor. Invest. New Drugs, 26, 45-51 (2008)
11. von Heideman A, Berglund Å, Larsson R, Nygren P. Safety and efficacy of NAD depleting cancer drugs: Results of a phase I clinical trial of CHS 828 and overview of published data. Cancer Chemother. Pharmacol., 65, 1165-1172 (2010)
12. Wosikowski K, Mattern K, Schemainda I, Hasmann M, Rattel B, Loser R. WK175, a novel antitumor agent, decreases the intracellular nicotinamide adenine dinucleotide concentration and induces the apoptotic cascade in human leukemia cells. Cancer Res., 62, 1057-1062 (2002)
13. Olesen UH, Christensen MK, Bjorkling F, Jaattela M, Jensen PB, Sehested M, Nielsen SJ. Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem. Biophys. Res. Commun., 367, 799-804 (2008)
14. Fujita S, Orita M. "Method of searching for ligand." pp. 1-19. Pub. No.: WO/2008/035729 International Application No.: PCT/ JP2007/068245 , cited 7 July, 2012
15. Khan JA, Tao X, Tong L. Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. Nat. Struct. Mol. Biol., 13, 582-588 (2006).
16. Elliott GC, Ajioka J, Okada CY. A rapid procedure for assaying nicotinamide phosphoribosyltransferase. Anal. Biochem., 107,199-205 (1980)
17. Pittelli M, Formentini L, Faraco G, Lapucci A, Rapizzi E, Cialdai F, Romano G, Moneti G, Moroni F, Chiarugi A. Inhibition of nicotinamide phosphoribosyltransferase: cellular bioenergetics reveals a mitochondrial insensitive NAD pool. J. Biol. Chem., 285, 34106- 34114 (2010)
18. Nahimana A, Attinger A, Aubry D, Greaney P, Ireson C, Thougaard AV, Tjornelund J, Dawson KM, Dupuis M, Duchosal MA. The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies. Blood, 113, 3276-3286 (2009)
19. Thakur BK, Dittrich T, Chandra P, Becker A, Kuehnau W, Klusmann JH, Reinhardt D, Welte K. Involvement of p53 in the cytotoxic activity of the NAMPT inhibitor FK866 in myeloid leukemic cells. Int. J. Cancer, 132, 766-774 (2013
20. Law JC, Ritke MK, Yalowich JC, Leder GH, Ferrell RE. Mutational inactivation of the p53 gene in the human erythroid leukemic K562 cell line. Leuk. Res., 17, 1045-1050 (1993)