Research Topics
| K W PankiewiczSummaryAffiliation: Pharmasset Inc Country: USA Publications
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Publications
Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemiaKrzysztof 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...- Fluorinated nucleosidesK W Pankiewicz
Pharmasset Inc, Atlanta, GA 30084, USA
Carbohydr Res 327:87-105. 2000..The synthesis and biological activity of deoxyfluoro nucleosides are reviewed... - The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide ribosideKrzysztof 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... - Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic targetKrzysztof 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... - Phosphonoxins: rational design and discovery of a potent nucleotide anti-Giardia agentDae 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... - Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitorLiqiang 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... - Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosisLaurent 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... - Recent development of IMP dehydrogenase inhibitors for the treatment of cancerLiqiang 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... - Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analoguesLiqiang 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)... - Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatmentLiqiang 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... - Efficient synthesis of benzamide riboside, a potential anticancer agentLaurent 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... - Probing binding requirements of NAD kinase with modified substrate (NAD) analoguesLaurent 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... - Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenaseDominik 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... - Inhibitors of the IMPDH enzyme as potential anti-bovine viral diarrhoea virus agentsLieven 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]... 
Dynamics of subgenomic hepatitis C virus replicon RNA levels in Huh-7 cells after exposure to nucleoside antimetabolitesLieven 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...- 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 activityPeiyuan 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... - Synthesis and anti-viral activity of a series of d- and l-2'-deoxy-2'-fluororibonucleosides in the subgenomic HCV replicon systemJunxing 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... - Design, synthesis, and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methylcytidine, a potent inhibitor of hepatitis C virus replicationJeremy 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... - Synthesis and in vitro anti-HCV activity of beta-D- and 1-2'-deoxy-2'-fluororibonucleosidesJunxing 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... - 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 agentsPeiyuan 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... 
Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenaseLiqiang 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...- Rational design and synthesis of novel nucleotide anti-Giardia agentsDae 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... - Nucleoside-5'-phosphoimidazolides: reagents for facile synthesis of dinucleoside pyrophosphatesLiqiang 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... - Synthesis of methylenebis(phosphonate) analogs of dinucleotide pyrophosphatesKrzysztof 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...