K W Pankiewicz

Summary

Affiliation: Pharmasset Inc
Country: USA

Publications

  1. ncbi request reprint Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia
    Krzysztof W Pankiewicz
    Pharmasset Inc, 1860 Montreal Road, Tucker, Georgia 30084, USA
    J Med Chem 45:703-12. 2002
  2. ncbi request reprint Fluorinated nucleosides
    K W Pankiewicz
    Pharmasset Inc, Atlanta, GA 30084, USA
    Carbohydr Res 327:87-105. 2000
  3. ncbi request reprint The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide riboside
    Krzysztof W Pankiewicz
    Pharmasset, Inc, 1860 Montreal Road, Tucker, Atlanta, GA 30084, USA
    Curr Med Chem 9:733-41. 2002
  4. ncbi request reprint Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target
    Krzysztof W Pankiewicz
    Pharmasset, Inc, Atlanta, GA 30084, USA
    Curr Med Chem 11:887-900. 2004
  5. ncbi request reprint Phosphonoxins: rational design and discovery of a potent nucleotide anti-Giardia agent
    Dae Hwan Suk
    Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:2811-6. 2007
  6. ncbi request reprint Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:3152-5. 2007
  7. ncbi request reprint Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis
    Laurent Bonnac
    Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:4588-91. 2007
  8. ncbi request reprint Recent development of IMP dehydrogenase inhibitors for the treatment of cancer
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA
    Curr Opin Drug Discov Devel 10:403-12. 2007
  9. ncbi request reprint Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Med Chem 50:5743-51. 2007
  10. ncbi request reprint Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis 55455, USA
    J Med Chem 50:6685-91. 2007

Collaborators

Detail Information

Publications24

  1. ncbi request reprint Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia
    Krzysztof W Pankiewicz
    Pharmasset Inc, 1860 Montreal Road, Tucker, Georgia 30084, USA
    J Med Chem 45:703-12. 2002
    ..These results show that C2-MAD and C4-MAD may be of therapeutic interest in the treatment of human leukemias...
  2. ncbi request reprint Fluorinated nucleosides
    K W Pankiewicz
    Pharmasset Inc, Atlanta, GA 30084, USA
    Carbohydr Res 327:87-105. 2000
    ..The synthesis and biological activity of deoxyfluoro nucleosides are reviewed...
  3. ncbi request reprint The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide riboside
    Krzysztof W Pankiewicz
    Pharmasset, Inc, 1860 Montreal Road, Tucker, Atlanta, GA 30084, USA
    Curr Med Chem 9:733-41. 2002
    ..The anti cancer activity of their synthetic dinucleotide analogues indicate that inactive compounds are not only poorly metabolized in cell but also are weak inhibitors of IMPDH as dinucleotides...
  4. ncbi request reprint Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target
    Krzysztof W Pankiewicz
    Pharmasset, Inc, Atlanta, GA 30084, USA
    Curr Med Chem 11:887-900. 2004
    ..Numerous novel inhibitors are under development. This review describes recent progress in the development of new drugs based on inhibition of IMP dehydrogenase...
  5. ncbi request reprint Phosphonoxins: rational design and discovery of a potent nucleotide anti-Giardia agent
    Dae Hwan Suk
    Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:2811-6. 2007
    ..Phosphonoxins, a new class of synthetic, rationally designed anti-microbial agents, are described. From this class a sub-micromolar inhibitor of Giardia trophozoite growth has been identified...
  6. ncbi request reprint Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:3152-5. 2007
    ..A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration...
  7. ncbi request reprint Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis
    Laurent Bonnac
    Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:4588-91. 2007
    ..The 4-phenoxy benzamide riboside (1) has been prepared as a key intermediate, converted into its 5'-mononucleotide (2), and coupled with AMP imidazolide to give the desired NAD analogue 3. It inhibits InhA with IC50 = 27 microM...
  8. ncbi request reprint Recent development of IMP dehydrogenase inhibitors for the treatment of cancer
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA
    Curr Opin Drug Discov Devel 10:403-12. 2007
    ..This article reviews recent applications of IMPDH inhibitors as anticancer agents, and highlights the progress that has been made in this field...
  9. ncbi request reprint Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Med Chem 50:5743-51. 2007
    ..Compound 38 [Ki = 16 nM (type I), Ki = 38 nM (type II)] inhibited proliferation of leukemic K562 cells (IC50 = 1.1 microM) more potently than tiazofurin (IC50 = 12.4 microM) or mycophenolic acid (IC50 = 7.7 microM)...
  10. ncbi request reprint Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment
    Liqiang Chen
    Center for Drug Design, University of Minnesota, Minneapolis 55455, USA
    J Med Chem 50:6685-91. 2007
    ..06 microM). Both MAHA (IC50=4.8 microM) and SAHA analogue 14 (IC50=7.7 microM) were more potent than parent compounds as antiproliferation agents. They were also significantly more potent as differentiation inducers...
  11. ncbi request reprint Efficient synthesis of benzamide riboside, a potential anticancer agent
    Laurent F Bonnac
    Center for Drug Design, University of Minnesota, 516 Delaware Street SE, Minneapolis, MN 55455, USA
    Nucleosides Nucleotides Nucleic Acids 26:1249-53. 2007
    ..An efficient five step synthesis of benzamide riboside (BR) amenable for a large scale synthesis has been developed. It allows for extensive pre-clinical studies of BR as a potential anticancer agent...
  12. ncbi request reprint Probing binding requirements of NAD kinase with modified substrate (NAD) analogues
    Laurent Bonnac
    Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:1512-5. 2007
    ..An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (K(i)=90 microM) of the human enzyme reported so far...
  13. ncbi request reprint Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase
    Dominik Rejman
    Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Med Chem 49:5018-22. 2006
    ..Both 8 and 13 (Ki = 20-87 nM) were found to be the most potent cofactor type inhibitors of IMP dehydrogenase...
  14. ncbi request reprint Inhibitors of the IMPDH enzyme as potential anti-bovine viral diarrhoea virus agents
    Lieven J Stuyver
    Pharmasset Inc, Tucker, GA, USA
    Antivir Chem Chemother 13:345-52. 2002
    ..However, in exponentially growing cells, they showed minimal toxicity at 100 microM over a 24 h period, but the toxicity was more pronounced after 3 days [50% cytotoxic concentration (CC50) value ranged from 5 to 30 microM]...
  15. pmc Dynamics of subgenomic hepatitis C virus replicon RNA levels in Huh-7 cells after exposure to nucleoside antimetabolites
    Lieven J Stuyver
    Pharmasset, Inc, Tucker, Georgia 30084, USA
    J Virol 77:10689-94. 2003
    ..cytostasis combined with a sharp decrease in replicon copy number per cell. These results suggest that high levels of CTP and UTP are critical parameters for maintaining the steady-state level replication of HCV replicon in Huh-7 cells...
  16. ncbi request reprint Synthesis of N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one, a novel compound with anti-hepatitis C virus activity
    Peiyuan Wang
    Pharmasset Inc, Tucker, Georgia 30084, Utah State University, Logan, Utah 84322, USA
    J Med Chem 47:6100-3. 2004
    ..A novel anti-hepatitis C virus (HCV) agent, N(3),5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridinin-5-one, was identified, and the structure was confirmed by chemical synthesis from 2-hydroxy-5-nitropyridine...
  17. ncbi request reprint Synthesis and anti-viral activity of a series of d- and l-2'-deoxy-2'-fluororibonucleosides in the subgenomic HCV replicon system
    Junxing Shi
    Pharmasset, Inc, 1860 Montreal Rd, Tucker, GA 30084, USA
    Bioorg Med Chem 13:1641-52. 2005
    ..All the l-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot always predict anti-HCV activity...
  18. ncbi request reprint Design, synthesis, and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methylcytidine, a potent inhibitor of hepatitis C virus replication
    Jeremy L Clark
    Pharmasset, Inc, 303 A College Road East, Princeton, New Jersey 08540, USA
    J Med Chem 48:5504-8. 2005
    ..Compound 1 shows increased inhibitory activity in the HCV replicon assay compared to 2'-C-methylcytidine and low cellular toxicity...
  19. ncbi request reprint Synthesis and in vitro anti-HCV activity of beta-D- and 1-2'-deoxy-2'-fluororibonucleosides
    Junxing Shi
    Pharmasset, Inc, Tucker, GA, USA
    Nucleosides Nucleotides Nucleic Acids 24:875-9. 2005
    ..All the L-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot reliably predict anti-HCV activity in vitro...
  20. ncbi request reprint Synthesis of N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one and its 3'-deoxysugar analogue as potential anti-hepatitis C virus agents
    Peiyuan Wang
    Department of Chemistry, Pharmasset, Inc, Tucker, GA 30084, USA
    Nucleosides Nucleotides Nucleic Acids 24:957-60. 2005
    ..It showed anti-HCV activity with EC50= 19.7 microM in replicon cells. Its 3'-deoxy sugar analogue was also synthesized, but was inactive against HCV in vitro...
  21. doi request reprint Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase
    Liqiang Chen
    Center for Drug Design, Academic Health Center, University of Minnesota, 516 Delaware Street S E, Minneapolis, MN 55455, USA
    Bioorg Med Chem 16:7462-9. 2008
    ..3-0.4 microM) than the corresponding parent bis(phosphonate)s 2 and 3 (K(i)=0.04-0.11 microM), respectively...
  22. ncbi request reprint Rational design and synthesis of novel nucleotide anti-Giardia agents
    Dae Hwan Suk
    Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA
    Bioorg Med Chem Lett 17:2064-7. 2007
    ..Design and synthesis of a novel nucleotide anti-Giardia agent that is micromolar inhibitor of Giardia trophozoite growth in culture is described...
  23. doi request reprint Nucleoside-5'-phosphoimidazolides: reagents for facile synthesis of dinucleoside pyrophosphates
    Liqiang Chen
    Center for Drug Design, The University of Minnesota, Minneapolis, Minnesota, USA
    Curr Protoc Nucleic Acid Chem . 2006
    ..The resulting compounds are useful for mechanistic studies of enzymes that use natural pyrophosphates as co-factors or substrates, and in development of inhibitors that have potential applications as therapeutic agents...
  24. doi request reprint Synthesis of methylenebis(phosphonate) analogs of dinucleotide pyrophosphates
    Krzysztof W Pankiewicz
    The University of Minnesota, Center for Drug Design, Minneapolis, Minnesota, USA
    Curr Protoc Nucleic Acid Chem . 2006
    ..The resulting compounds are useful for mechanistic studies of enzymes that use the natural pyrophosphates as cofactors or substrates, and in development of inhibitors that have potential applications as therapeutic agents...