Research Topics
Species | Phillip A FurmanSummaryAffiliation: Pharmasset Inc Country: USA Publications
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Publications
Nucleoside analog inhibitors of hepatitis C viral replication: recent advances, challenges and trendsPhillip A Furman
Pharmasset, Inc, Princeton, NJ 08540, USA
Future Med Chem 1:1429-52. 2009..Herein, we discuss various classes of nucleoside inhibitors, with a focus on available structure-activity relationships, their mode of action and resistance profile...- Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virusMichael J Sofia
Pharmasset, Inc, 303A College Road East, Princeton, New Jersey 08540, USA
J Med Chem 53:7202-18. 2010..51 (PSI-7977) was selected as a clinical development candidate... 
Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661Phillip A Furman
Pharmasset, Inc, Princeton, NJ 08540, USA
Antiviral Res 91:120-32. 2011..PSI-352666 is equally active against wild-type NS5B and NS5B containing the S282T amino acid alteration...- β-D-2'-α-F-2'-β-C-Methyl-6-O-substituted 3',5'-cyclic phosphate nucleotide prodrugs as inhibitors of hepatitis C virus replication: a structure-activity relationship studyJinfa Du
Pharmasset, Inc, Princeton 303A College Road East, Princeton, NJ 08540, USA
Bioorg Med Chem Lett 22:5924-9. 2012..Compounds 12, 13 and 19 also demonstrated the ability to effectively deliver in vivo high levels of active nucleoside phosphates to rat liver... - PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replicationAngela M Lam
Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
Antimicrob Agents Chemother 54:3187-96. 2010..Clearance studies using replicon cells demonstrated that PSI-7851 was able to clear cells of HCV replicon RNA and prevent viral rebound... - Inhibition of hepatitis C virus replicon RNA synthesis by PSI-352938, a cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosineAngela M Lam
Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
Antimicrob Agents Chemother 55:2566-75. 2011..PSI-352938 is currently being evaluated in a phase I clinical study in genotype 1-infected individuals... - Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNAAngela M Lam
Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
J Virol 85:12334-42. 2011.... - Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977Eisuke Murakami
Pharmasset, Inc, Princeton, New Jersey 08540, USA
J Biol Chem 285:34337-47. 2010..PSI-7411 is then consecutively phosphorylated to the diphosphate, PSI-7410, and to the active triphosphate metabolite, PSI-7409, by UMP-CMP kinase and nucleoside diphosphate kinase, respectively... - Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virusAngela M Lam
Pharmasset, Inc, Princeton, New Jersey, USA
Antimicrob Agents Chemother 56:3359-68. 2012.... - Phosphoramidate prodrugs of (-)-β-D-(2R,4R)-dioxolane-thymine (DOT) as potent anti-HIV agentsPeiyuan Wang
Pharmasset, Inc, Princeton, NJ, USA
Antivir Chem Chemother 22:217-38. 2012..D-(2R,4R)-dioxolane-thymine (DOT) is a thymidine analogue that is active against wild-type and NRTI-resistant HIV-1 mutants. It has been shown that the anti-HIV activity of DOT is limited due to poor monophosphorylation... - Synthesis of stable isotope labeled analogs of the anti-hepatitis C virus nucleotide prodrugs PSI-7977 and PSI-352938Byoung Kwon Chun
Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
Nucleosides Nucleotides Nucleic Acids 30:886-96. 2011..As expected, these 2 '-C-(trideuterated-(13)C-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones... - A 2'-deoxy-2'-fluoro-2'-C-methyl uridine cyclopentyl carbocyclic analog and its phosphoramidate prodrug as inhibitors of HCV NS5B polymeraseJian Liu
Pharmasset, Inc, Princeton, New Jersey 08540, USA
Nucleosides Nucleotides Nucleic Acids 31:277-85. 2012..This lack of activity might be attributed to the inability of the monophosphate to be converted to the corresponding diphosphate or triphosphate or the inactivity of triphosphate of 11 as an inhibitor of the polymerase... - The mechanism of action of beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine involves a second metabolic pathway leading to beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymeraseEisuke Murakami
Pharmasset, Inc, 303 A College Road East, Princeton, NJ 08540, USA
Antimicrob Agents Chemother 52:458-64. 2008..RO2433-TP is a potent inhibitor of the HCV RdRp; however, both enzymatic and cell-based assays show that PSI-6130 triphosphate is a more potent inhibitor of the HCV RdRp than RO2433-TP... - Evaluation of the in vitro anti-HBV activity of clevudine in combination with other nucleoside/nucleotide inhibitorsCongrong Niu
Pharmasset, Inc, Princeton, NJ, USA
Antivir Ther 15:401-12. 2010..We investigated the activity of clevudine (CLV) in combination with other nucleoside/nucleotide analogues to determine if these combinations were compatible in vitro... - Metabolic activation of the anti-hepatitis C virus nucleotide prodrug PSI-352938Congrong Niu
Pharmasset, Inc, Princeton, New Jersey, USA
Antimicrob Agents Chemother 56:3767-75. 2012..Since CYP3A4 is highly expressed in the liver, the CYP3A4-dependent metabolism of PSI-352938 makes it an effective liver-targeted prodrug, in part accounting for the potent antiviral activity observed clinically... - Mechanism of activation of beta-D-2'-deoxy-2'-fluoro-2'-c-methylcytidine and inhibition of hepatitis C virus NS5B RNA polymeraseEisuke Murakami
Pharmasset, Inc, 303A College Road East, Princeton, NJ 08640, USA
Antimicrob Agents Chemother 51:503-9. 2007..Incorporation of PSI-6130-MP into RNA catalyzed by purified NS5B RNA polymerase resulted in chain termination... - Synthesis and anti-HCV activity of 3',4'-oxetane nucleosidesWonsuk Chang
Pharmasset, Inc, East, Princeton, NJ 08540, USA
Bioorg Med Chem Lett 20:4539-43. 2010..Lack of anti-HCV activity in the replicon assay may be due to the inability of the monophosphates to be converted to their corresponding diphosphates... - Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimeticsWonsuk Chang
Pharmasset, Inc, Princeton, NJ 08540, USA
Bioorg Med Chem Lett 22:2938-42. 2012.... 
Inhibition of hepatitis C replicon RNA synthesis by beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine: a specific inhibitor of hepatitis C virus replicationLieven J Stuyver
Pharmasset Inc, Princeton, NJ, USA
Antivir Chem Chemother 17:79-87. 2006..Finally, the no-effect dose for mice treated intraperitoneally with PSI-6130 for six consecutive days was > or =100 mg/kg per day...- Phenylpropenamide derivatives: anti-hepatitis B virus activity of the Z isomer, SAR and the search for novel analogsPeiyuan Wang
Pharmasset, Inc, Princeton, NJ 08540, USA
Bioorg Med Chem Lett 21:4642-7. 2011..5 μM in vitro. Attempts to develop ring constrained analogs did not lead to active HBV inhibitors... - Adenosine deaminase-like protein 1 (ADAL1): characterization and substrate specificity in the hydrolysis of N(6)- or O(6)-substituted purine or 2-aminopurine nucleoside monophosphatesEisuke Murakami
Pharmasset, Inc, 303A College Road East, Princeton, New Jersey 08540, USA
J Med Chem 54:5902-14. 2011..Furthermore, amino acid sequence analysis in conjunction with crystallographic data and metal analysis suggested that ADAL1 contains a catalytic zinc ion. Finally, a potential physiological role of ADAL1 is discussed... - Clevudine is efficiently phosphorylated to the active triphosphate form in primary human hepatocytesCongrong Niu
Pharmasset, Inc, Princeton, NJ 08540, USA
Antivir Ther 13:263-9. 2008..Human hepatoma cell lines are the only liver-derived cells in which CLV metabolism has been investigated. Here, we examine CLV metabolism in primary human hepatocytes, which better represent CLV metabolism in the liver... - 2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: discovery of PSI-352938P Ganapati Reddy
Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
Bioorg Med Chem Lett 20:7376-80. 2010..These studies ultimately led to the selection of the clinical development candidate 24a (PSI-352938)... - Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine as an anti-HIV agentEisuke Murakami
Pharmasset Inc, Princeton, NJ, USA
Antivir Chem Chemother 18:83-92. 2007..Little or no resistance was observed with the enzymes harbouring mutations resistant to lamivudine (M184V) and non-nucleoside RT inhibitors (K103N)... - 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... - Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analysesJerry L Jeffrey
Triangle Pharmaceuticals, Inc, a subsidiary of Gilead Sciences, Durham, North Carolina 27717, USA
J Biol Chem 278:18971-9. 2003..Overall, the enzymatic data correlated well with the antiviral data obtained from cell culture experiments and further supported the use of amdoxovir for the treatment of nucleoside reverse transcriptase inhibitor-experienced patients...