Robert A Fridell

Summary

Affiliation: Bristol-Myers Squibb
Country: USA

Publications

  1. pmc Intragenic complementation of hepatitis C virus NS5A RNA replication-defective alleles
    Robert A Fridell
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    J Virol 87:2320-9. 2013
  2. pmc Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system
    Robert A Fridell
    Department of Virology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Antimicrob Agents Chemother 54:3641-50. 2010
  3. pmc Distinct functions of NS5A in hepatitis C virus RNA replication uncovered by studies with the NS5A inhibitor BMS-790052
    Robert A Fridell
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    J Virol 85:7312-20. 2011
  4. ncbi request reprint Hepatitis C virus NS5A replication complex inhibitors. Part 6: Discovery of a novel and highly potent biarylimidazole chemotype with inhibitory activity toward genotypes 1a and 1b replicons
    Makonen Belema
    Departments of Discovery Chemistry, Virology, Lead Discovery and Optimization, Computer Assisted Drug Design, and Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States
    J Med Chem 57:1995-2012. 2014
  5. pmc Hepatitis C virus RNA elimination and development of resistance in replicon cells treated with BMS-790052
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 56:1350-8. 2012
  6. pmc Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 57:2054-65. 2013
  7. pmc In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 56:1588-90. 2012
  8. doi request reprint HCV NS5A replication complex inhibitors. Part 5: discovery of potent and pan-genotypic glycinamide cap derivatives
    Makonen Belema
    Department of Medicinal Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 23:4428-35. 2013
  9. doi request reprint Characterizations of HCV NS5A replication complex inhibitors
    Donald R O'Boyle Ii
    Bristol Myers Squibb Research and Development, Department of Virology Discovery, 5 Research Parkway, Wallingford, CT 06492, USA
    Virology 444:343-54. 2013
  10. pmc In vitro activity of daclatasvir on hepatitis C virus genotype 3 NS5A
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 57:611-3. 2013

Collaborators

Detail Information

Publications20

  1. pmc Intragenic complementation of hepatitis C virus NS5A RNA replication-defective alleles
    Robert A Fridell
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    J Virol 87:2320-9. 2013
    ..We postulate that these complementation groups define three distinct and genetically separable functions of NS5A in RNA replication...
  2. pmc Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system
    Robert A Fridell
    Department of Virology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Antimicrob Agents Chemother 54:3641-50. 2010
    ..Importantly, BMS-790052-resistant variants remained fully sensitive to alpha interferon and small-molecule inhibitors of HCV protease and polymerase...
  3. pmc Distinct functions of NS5A in hepatitis C virus RNA replication uncovered by studies with the NS5A inhibitor BMS-790052
    Robert A Fridell
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    J Virol 85:7312-20. 2011
    ..Our data indicate that BMS-790052 blocks the cis-acting function of NS5A. Since BMS-790052 also impairs JFH1 NS5A hyperphosphorylation, it likely also blocks the trans-acting function...
  4. ncbi request reprint Hepatitis C virus NS5A replication complex inhibitors. Part 6: Discovery of a novel and highly potent biarylimidazole chemotype with inhibitory activity toward genotypes 1a and 1b replicons
    Makonen Belema
    Departments of Discovery Chemistry, Virology, Lead Discovery and Optimization, Computer Assisted Drug Design, and Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States
    J Med Chem 57:1995-2012. 2014
    ..Securing potent GT-1a activity in a chemotype class lacking overt structural liabilities was a critical milestone in the effort to realize the full clinical potential of targeting the HCV NS5A protein. ..
  5. pmc Hepatitis C virus RNA elimination and development of resistance in replicon cells treated with BMS-790052
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 56:1350-8. 2012
    ..Insights gained from the in vitro anti-HCV activity and resistance profiles of BMS-790052 will be used to help guide the clinical development of this novel HCV inhibitor...
  6. pmc Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 57:2054-65. 2013
    ..After the end of DCV treatment, viral fitness, rather than DCV resistance, probably determines which viral variants emerge as dominant in populations...
  7. pmc In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 56:1588-90. 2012
    ..NS5A residue 30 was an important site for BMS-790052-selected resistance in the hybrid replicons. Our results support the potential of BMS-790052 as a valuable component of combination therapy for HCV genotype-4 chronic infection...
  8. doi request reprint HCV NS5A replication complex inhibitors. Part 5: discovery of potent and pan-genotypic glycinamide cap derivatives
    Makonen Belema
    Department of Medicinal Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 23:4428-35. 2013
    ....
  9. doi request reprint Characterizations of HCV NS5A replication complex inhibitors
    Donald R O'Boyle Ii
    Bristol Myers Squibb Research and Development, Department of Virology Discovery, 5 Research Parkway, Wallingford, CT 06492, USA
    Virology 444:343-54. 2013
    ..The functional data supports a model of inhibition that implicates inhibitor binding by covalently combining distinct pharmacophores across an NS5A dimer interface to achieve maximal inhibition of HCV replication. ..
  10. pmc In vitro activity of daclatasvir on hepatitis C virus genotype 3 NS5A
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 57:611-3. 2013
    ..Selection studies with a hybrid HCV3a replicon identified NS5A residues 31 and 93 as sites for DCV-selected resistance. Our results support the potential use of DCV as a component in combination therapies for HCV3a chronic infection...
  11. ncbi request reprint Genotypic and phenotypic analysis of variants resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor BMS-790052 in humans: in vitro and in vivo correlations
    Robert A Fridell
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, CT 06492, USA
    Hepatology 54:1924-35. 2011
    ..e., fitness) of the variants...
  12. ncbi request reprint Hepatitis C virus NS5A replication complex inhibitors: the discovery of daclatasvir
    Makonen Belema
    Departments of Discovery Chemistry, Discovery Chemistry Synthesis, Computer Assisted Drug Design, and Pharmaceutical Candidate Optimization, Virology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States
    J Med Chem 57:2013-32. 2014
    ....
  13. ncbi request reprint Discovery and development of hepatitis C virus NS5A replication complex inhibitors
    Makonen Belema
    Department of Discovery Chemistry, Department of Virology Discovery, and Department of Computer Assisted Drug Design, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States
    J Med Chem 57:1643-72. 2014
    ..We conclude with a synopsis of the results of notable clinical trials with HCV NS5A RCIs. ..
  14. doi request reprint Impact of a baseline polymorphism on the emergence of resistance to the hepatitis C virus nonstructural protein 5A replication complex inhibitor, BMS-790052
    Jin Hua Sun
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, CT, USA
    Hepatology 55:1692-9. 2012
    ..A BL polymorphism (E62D) did not contribute resistance to BMS-790052; however, the linked variant, Q30R-E62D, conferred high-level resistance in vitro and is likely responsible for VBT in vivo...
  15. doi request reprint HCV NS5A replication complex inhibitors. Part 3: discovery of potent analogs with distinct core topologies
    Omar D Lopez
    Department of Medicinal Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 23:779-84. 2013
    ....
  16. doi request reprint Synthesis and SAR studies of novel heteroaryl fused tetracyclic indole-diamide compounds: potent allosteric inhibitors of the hepatitis C virus NS5B polymerase
    Min Ding
    Molecular Sciences and Candidate Optimization, Bristol Myers Squibb, Research and Development, Wallingford, CT 06492, United States
    Bioorg Med Chem Lett 22:2866-71. 2012
    ....
  17. pmc Comparison of Daclatasvir Resistance Barriers on NS5A from Hepatitis C Virus Genotypes 1 to 6: Implications for Cross-Genotype Activity
    Chunfu Wang
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, Connecticut, USA
    Antimicrob Agents Chemother 58:5155-63. 2014
    ..The in vitro data suggest that DCV has the potential to be an effective agent for HCV genotypes 1 to 6 when used in combination therapy. ..
  18. doi request reprint The effects of NS5A inhibitors on NS5A phosphorylation, polyprotein processing and localization
    Dike Qiu
    Department of Virology, Bristol Myers Squibb Research and Development, Wallingford, CT, USA
    J Gen Virol 92:2502-11. 2011
    ..Collectively, our results suggest that NS5A inhibitors probably impact several aspects of HCV expression and regulation. These findings may help to explain the exceptional potency of this class of HCV replication complex inhibitors...
  19. doi request reprint Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
    Min Gao
    Department of Virology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    Nature 465:96-100. 2010
    ....
  20. doi request reprint The synthesis of novel heteroaryl-fused 7,8,9,10-tetrahydro-6H-azepino[1,2-a]indoles, 4-oxo-2,3-dihydro-1H-[1,4]diazepino[1,7-a]indoles and 1,2,4,5-tetrahydro-[1,4]oxazepino[4,5-a]indoles. Effective inhibitors of HCV NS5B polymerase
    Min Ding
    Discovery Chemistry, Research and Development, Bristol Myers Squibb Co, 5 Research Parkway, Wallingford, CT 06492, USA
    Org Biomol Chem 9:6654-62. 2011
    ..The hepatitis C virus (HCV) non-structural 5B (NS5B) polymerase inhibitory activities of select examples from each molecular class are briefly presented...