Biocatalytic synthesis and structure elucidation of cyclized metabolites of the deacetylase inhibitor panobinostat (LBH589)

Drug Metabolism and Disposition

Volumn 40, Issue 5, 2012, Pages 1041-1050

  Fredenhagen, Andreas ^a   Kittelmann, Matthias ^a   Oberer, Lukas ^a   Kuhn, Anton ^a   Kühnöl, Jürgen ^a   Délémonté, Thierry ^a   Aichholz, Reiner ^a   Wang, Ping ^b   Atadja, Peter ^c   Shultz, Michael D ^b  

^a NOVARTIS PHARMA AG   (Switzerland)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^c China Novartis Institutes for BioMedical Research   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DRUG METABOLITE; PANOBINOSTAT; RECOMBINANT ENZYME;

ANALYTIC METHOD; ARTICLE; BIOCATALYSIS; BIOTRANSFORMATION; CYCLIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ESCHERICHIA COLI; IN VITRO STUDY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL;

ANTINEOPLASTIC AGENTS; BIOCATALYSIS; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYCLIZATION; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; ESCHERICHIA COLI; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; MOLECULAR CONFORMATION; TANDEM MASS SPECTROMETRY;

ESCHERICHIA COLI;

EID: 84859922839     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.043620     Document Type: Article

References (31)

1. Agozzino P, Avellone G, Bongiorno D, Ceraulo L, Filizzola F, Natoli MC, Livrea MA, and Tesoriere L (2003) Melatonin: structural characterization of its non-enzymatic monooxygenate metabolite. J Pineal Res 35:269-275. (Pubitemid 37338861)
2. Atadja P (2009) Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett 280:233-241.
3. Blake JA, Pritchard M, Ding S, Smith GC, Burchell B, Wolf CR, and Friedberg T (1996) Coexpression of human P450 (CYP3A4) and P450 reductase generates a highly functional monooxygenase system in Escherichia coli. FEBS Lett 397:210-214. (Pubitemid 26414019)
4. Bolden JE, Peart MJ, and Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769-784. (Pubitemid 44348499)
5. Hong H, Caceres-Cortes J, Su H, Huang X, Roongta V, Bonacorsi S Jr, Hong Y, Tian Y, Iyer RA, Humphreys WG, et al. (2011) Mechanistic studies on a P450-mediated rearrangement of BMS-690514: conversion of a pyrrolotriazine to a hydroxypyridotriazine. Chem Res Toxicol 24:125-134.
6. Lee YS, Lim KH, Guo X, Kawaguchi Y, Gao Y, Barrientos T, Ordentlich P, Wang XF, Counter CM, and Yao TP (2008) The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis. Cancer Res 68:7561-7569.
7. Li M, Conrad B, Maus RG, Pitzenberger SM, Subramanian R, Fang X, Kinzer JA, and Perpall HJ (2005) A novel oxidative degradation pathway of indomethacin under the stressing by hydrogen peroxide. Tetrahedron Lett 46:3533-3536. (Pubitemid 40585587)
8. Kamel A, Obach RS, Colizza K, Wang W, O'Connell TN, Coelho RV Jr, Kelley RM, and Schildknegt K (2010) Metabolism, pharmacokinetics, and excretion of the 5-hydroxytryptamine1B receptor antagonist elzasonan in humans. Drug Metab Dispos 38: 1984-1999.
9. Kelly SL, Lamb DC, Jackson CJ, Warrilow AG, and Kelly DE (2003) The biodiversity of microbial cytochromes P450. Adv Microb Physiol 47:131-186. (Pubitemid 37214150)
10. Komuro M, Higuchi T, and Hirobe M (1996) Application of chemical P-450 model systems to studies on drug metabolism. Part X. Novel hydroxylactonization of γ,δ- and β,γ-unsaturated carboxylic acids with an iron porphyrin-iodosylbenzene system. J Chem Soc 1:2309-2313. (Pubitemid 126810856)
11. Marks PA, Richon VM, and Rifkind RA (2000) Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst 92:1210-1216. (Pubitemid 30627729)
12. Nakagawa M, Kato S, Kataoka S, Kodato S, Watanabe H, Okajima H, Hino T, and Witkop B (1981) Dye-sensitized photooxygenation of tryptophan: 3a-hydroperoxypyrroloindole as a labile precursor of formylkynurenine. Chem Pharm Bull 29:1013-1026.
13. Nguyen NT, Wrona MZ, and Dryhurst G (1986a) Peroxidase-catalyzed and electrochemical oxidation of L-tryptophan. Bioelectrochem Bioenerg 15:257-274.
14. Nguyen NT, Wrona MZ, and Dryhurst G (1986b) Electrochemical oxidation of tryptophan. J Electroanal Chem Interface 199:101-126.
15. Prince HM, Bishton MJ, and Johnstone RW (2009) Panobinostat (LBH589): a potent pandeacetylase inhibitor with promising activity against hematologic and solid tumors. Future Oncol 5:601-612.
16. Pritchard MP, Ossetian R, Li DN, Henderson CJ, Burchell B, Wolf CR, and Friedberg T (1997) A general strategy for the expression of recombinant human cytochrome P450s in Escherichia coli using bacterial signal peptides: expression of CYP3A4, CYP2A6, and CYP2E1. Arch Biochem Biophys 345:342-354. (Pubitemid 27400630)
17. Pritchard MP, Glancey MJ, Blake JA, Gilham DE, Burchell B, Wolf CR, and Friedberg T (1998) Functional co-expression of CYP2D6 and human NADPH-cytochrome P450 reductase in Escherichia coli. Pharmacogenetics 8:33-42. (Pubitemid 28097599)
18. Prokai L, Prokai-Tatrai K, Pop E, Bodor N, Lango J, and Roboz J (1993) Fast atom bombardment and tandem mass spectrometry of quaternary pyridinium salt-type tryptophan derivatives. Org Mass Spectrom 28:707-715.
19. Ramanathan R, Josephs JL, Jemal M, Arnold M, and Humphreys WG (2010) Novel MS solutions inspired by MIST. Bioanalysis 2:1291-1313.
20. 1Δg)-derived oxidation products of tryptophan: a combination of tandem mass spectrometry analyses and isotopic labeling studies. J Am Soc Mass Spectrom 20:188-197.
21. Sambucetti LC, Fischer DD, Zabludoff S, Kwon PO, Chamberlin H, Trogani N, Xu H, and Cohen D (1999) Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem 274:34940-34947. (Pubitemid 129509542)
22. Savige WE (1975) New oxidation products of tryptophan. Aust J Chem 28:2275-2287.
23. Schroer K, Kittelmann M, and Lütz S (2010) Recombinant human cytochrome P450 monooxygenases for drug metabolite synthesis. Biotechnol Bioeng 106:699-706.
24. Shultz MD, Cao X, Chen CH, Cho YS, Davis NR, Eckman J, Fan J, Fekete A, Firestone B, Flynn J, et al. (2011) Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors. J Med Chem 54:4752-4772.
25. + metastable ions. Org Mass Spectrom 7:1173-1177.
26. Tan DX, Manchester LC, Reiter RJ, Plummer BF, Hardies LJ, Weintraub ST, Vijayalaxmi, and Shepherd AM (1998) A novel melatonin metabolite, cyclic 3-hydroxymelatonin: a biomarker of in vivo hydroxyl radical generation. Biochem Biophys Res Commun 253:614-620. (Pubitemid 29039192)
27. Voice MW, Zhang Y, Wolf CR, Burchell B, and Friedberg T (1999) Effects of human cytochrome b5 on CYP3A4 activity and stability in vivo. Arch Biochem Biophys 366:116-124. (Pubitemid 29394236)
28. Williams RM (2002) Total synthesis and biosynthesis of paraherquamides: an intriguing story of the biological Diels-Alder construction. Chem Pharm Bull 50:711-740.
29. Yang XY, Haug C, Yang YP, He ZS, and Ye Y (2003) Stereoselective synthesis of syn- and anti-3a-hydroxyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b] indole-2-carboxylic acid. Chin Chem Lett 14:130-132. (Pubitemid 36332533)
30. Zain J, Kaminetzky D, and O'Connor OA (2010) Emerging role of epigenetic therapies in cutaneous T-cell lymphomas. Expert Rev Hematol 3:187-203.
31. Zhang Z, Chen Q, Li Y, Doss GA, Dean BJ, Ngui JS, Elipe MS, Kim S, Wu JY, DiNinno F, et al. (2005) In vitro bioactivation of dihydrobenzoxathiin selective estrogen receptor modulators by cytochrome P450 3A4 in human liver microsomes: formation of reactive iminium and quinone type metabolites. Chem Res Toxicol 18:675-685. (Pubitemid 40563281)