The pharmacokinetics, toxicities, and biologic effects of FK866, a nicotinamide adenine dinucleotide biosynthesis inhibitor

Kyle D. Holen1, Leonard B. Saltz2, Ellen Hollywood2, K. Bürk3, Axel-Rainer Hanauske4
1University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University Hospital and Clinics, Madison, USA
2Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA
3ClinDescience GmbH Gabelsbergerstraße 36, Munich, Germany
4Asklepios Hospital St. Georg, Hamburg, Germany

Tóm tắt

Từ khóa


Tài liệu tham khảo

Martin DS, Schwartz GK (1997) Chemotherapeutically induced DNA Damage, ATP depletion, and the apoptotic biochemical cascade. Oncol Res 9:1–5

Komatsu N, Nakagawa M, Oda T, Muramatsu T (2000) Depletion of intracellular NAD+ and ATP levels during ricin-induced apoptosis through the specific ribosomal inactivation results in the cytolysis of U937 cells. J Biochem (Tokyo) 128:463–470

Wielckens K, Schmidt A, George E, Bredehosrt R, Hilz H (1982) DNA fragmentation and NAD depletion. Their relation to the turnover of endogenous mono(ADP-ribosyl) and poly (ADP-ribosyl) proteins. J Biol Chem 257:12872–12877

Alano CC, Ying W, Swanson RA (2004) Poly(ADP-ribose) polymerase-1-mediated cell death in astrocytes requires NAD+ depletion and mitochondrial permeability transition. J Biol Chem 279:18895–18902

Du L, Zhang X, Han YY, Burke NA, Kochanek PM, Watkins SC, Graham SH, Carcillo JA, Szabo C, Clark RS (2003) Intra-mitochondrial poly(ADP-ribosylation) contributes to NAD+ depletion and cell death induced by oxidative stress. J Biol Chem 278:18426–18433

Heller B, Burkle A, Radons J, Fengler E, Muller M, Burkart V, Kolb H (1997) DNA-damage and NAD(+)-depletion are initial events in oxygen radical induced islet cell death. Adv Exp Med Biol 426:329–334

Stubberfield CR, Cohen GM (1988) NAD+ depletion and cytotoxicity in isolated hepatocytes. Biochem Pharmacol 37:3967–3974

Jacobson MK, Twehous D, Hurley LH (1986) Depletion of nicotinamide adenine dinucleotide in normal and xeroderma pigmentosum fibroblast cells by the antitumor drug CC-1065. Biochem 25:5929–5932

Alvarez-Gonzalez R, Eichenberger R, Althaus FR (1986) Poly(ADP-ribose) biosynthesis and suicidal NAD+ depletion following carcinogen exposure of mammalian cells. Molec Cell Biol Res Commun 138:1051–1057

Wosikowski K, Mattern K, Schemainda I, Hasmann M, Rattel B, Loser R (2002) WK175, a novel antitumor agent, decreases the intracellular nicotinamide adenine dinucleotide concentration and induces the apopototic cascade in human leukemia cells. Cancer Res 62:1057–1062

Hasmann M, Schemainda I (2003) FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res 63:7436–7442

Drevs J, Loser R, Rattel B, Esser N (2003) Antiangiogenic potency of FK866/K22.175, a new inhibitor of intracellular NAD biosynthesis, in murine renal cell carcinoma. Anticancer Res 23:4853–4858

Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214

Muruganandham M, Alfieri AA, Matei C, Chen Y, Sukenick G, Schemainda I, Hasmann M, Saltz LB, Koutcher JA (2005) Metabolic signatures associated with a NAD synthesis inhibitor-induced tumor apoptosis identified by 1H-decoupled-31P magnetic resonance spectroscopy. Clin Cancer Res 11:3503–3513