Gabriel Birkus

Summary

Affiliation: Gilead Sciences
Country: USA

Publications

  1. pmc Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131
    Gabriel Birkus
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 51:543-50. 2007
  2. pmc Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*
    Gabriel Birkus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
    Antimicrob Agents Chemother 46:1610-3. 2002
  3. pmc Role of cathepsin A and lysosomes in the intracellular activation of novel antipapillomavirus agent GS-9191
    Gabriel Birkus
    Biology Department, Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 55:2166-73. 2011
  4. doi request reprint Activation of 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino] phenoxyphosphinyl]-methoxy]propyl]adenine (GS-7340) and other tenofovir phosphonoamidate prodrugs by human proteases
    Gabriel Birkus
    Gilead Sciences, Inc, 362 Lakeside Drive, Foster City, CA 94404, USA
    Mol Pharmacol 74:92-100. 2008
  5. pmc GS-9191 is a novel topical prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine with antiproliferative activity and possible utility in the treatment of human papillomavirus lesions
    Grushenka H I Wolfgang
    Gilead Sciences, 333 Lakeside Drive, Foster City, CA, USA
    Antimicrob Agents Chemother 53:2777-84. 2009
  6. doi request reprint Sugar-modified derivatives of cytostatic 7-(het)aryl-7-deazaadenosines: 2'-C-methylribonucleosides, 2'-deoxy-2'-fluoroarabinonucleosides, arabinonucleosides and 2'-deoxyribonucleosides
    Petr Naus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam 2, CZ 16610 Prague 6, Czech Republic
    Bioorg Med Chem 20:5202-14. 2012
  7. ncbi request reprint Tenofovir exhibits low cytotoxicity in various human cell types: comparison with other nucleoside reverse transcriptase inhibitors
    Tomas Cihlar
    Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antiviral Res 54:37-45. 2002
  8. doi request reprint Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148
    Richard L Mackman
    Department of Medicinal Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA94404, USA
    Bioorg Med Chem 18:3606-17. 2010
  9. doi request reprint CycloSal-phosphate pronucleotides of cytostatic 6-(Het)aryl-7-deazapurine ribonucleosides: Synthesis, cytostatic activity, and inhibition of adenosine kinases
    Pavla Spácilová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Prague, Czech Republic
    ChemMedChem 5:1386-96. 2010
  10. ncbi request reprint The substrate activity of (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine diphosphate toward DNA polymerases alpha, delta and epsilon
    Gabriel Birkus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Antivir Chem Chemother 15:23-33. 2004

Collaborators

Detail Information

Publications17

  1. pmc Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131
    Gabriel Birkus
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 51:543-50. 2007
    ..Collectively, these data demonstrate the key role of CatA in the intracellular activation of nucleotide phosphonoamidate prodrugs and open new possibilities for further improvement of this important class of antiviral prodrugs...
  2. pmc Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*
    Gabriel Birkus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
    Antimicrob Agents Chemother 46:1610-3. 2002
    ..2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively...
  3. pmc Role of cathepsin A and lysosomes in the intracellular activation of novel antipapillomavirus agent GS-9191
    Gabriel Birkus
    Biology Department, Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 55:2166-73. 2011
    ....
  4. doi request reprint Activation of 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino] phenoxyphosphinyl]-methoxy]propyl]adenine (GS-7340) and other tenofovir phosphonoamidate prodrugs by human proteases
    Gabriel Birkus
    Gilead Sciences, Inc, 362 Lakeside Drive, Foster City, CA 94404, USA
    Mol Pharmacol 74:92-100. 2008
    ....
  5. pmc GS-9191 is a novel topical prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine with antiproliferative activity and possible utility in the treatment of human papillomavirus lesions
    Grushenka H I Wolfgang
    Gilead Sciences, 333 Lakeside Drive, Foster City, CA, USA
    Antimicrob Agents Chemother 53:2777-84. 2009
    ..At the highest dose (0.1%), cures were evident at the end of 5 weeks, and lesions did not recur in a 30-day follow-up period. These data suggest that GS-9191 may have utility in the treatment of HPV-induced lesions...
  6. doi request reprint Sugar-modified derivatives of cytostatic 7-(het)aryl-7-deazaadenosines: 2'-C-methylribonucleosides, 2'-deoxy-2'-fluoroarabinonucleosides, arabinonucleosides and 2'-deoxyribonucleosides
    Petr Naus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam 2, CZ 16610 Prague 6, Czech Republic
    Bioorg Med Chem 20:5202-14. 2012
    ..The most active was 7-ethynyl-7-deazaadenine fluoroarabinonucleoside which showed submicromolar antiproliferative activity. However, all the sugar-modified derivatives were less active than the parent ribonucleosides...
  7. ncbi request reprint Tenofovir exhibits low cytotoxicity in various human cell types: comparison with other nucleoside reverse transcriptase inhibitors
    Tomas Cihlar
    Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antiviral Res 54:37-45. 2002
    ..In conclusion, tenofovir exhibited weak cytotoxic effects in all cell types tested with less in vitro cytotoxicity than the majority of NRTIs currently used for the treatment of HIV disease...
  8. doi request reprint Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148
    Richard L Mackman
    Department of Medicinal Chemistry, Gilead Sciences, 333 Lakeside Drive, Foster City, CA94404, USA
    Bioorg Med Chem 18:3606-17. 2010
    ..Following oral dosing (3mg/kg) in Beagle dogs, high levels (>9.0microM) of active metabolite 15 were observed in PBMCs, validating the prodrug design process and leading to the nomination of 5 as a clinical candidate...
  9. doi request reprint CycloSal-phosphate pronucleotides of cytostatic 6-(Het)aryl-7-deazapurine ribonucleosides: Synthesis, cytostatic activity, and inhibition of adenosine kinases
    Pavla Spácilová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Prague, Czech Republic
    ChemMedChem 5:1386-96. 2010
    ..The presence of a cycloSal-phosphate group also influenced selectivity toward various cell lines. Several pronucleotides were found which strongly inhibit human adenosine kinase but only weakly inhibit the MTB adenosine kinase...
  10. ncbi request reprint The substrate activity of (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine diphosphate toward DNA polymerases alpha, delta and epsilon
    Gabriel Birkus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Antivir Chem Chemother 15:23-33. 2004
    ..These observations indicate that interaction of HPMPApp with pol alpha, delta and epsilon may contribute to its cellular toxicity and explain its antiviral activity against polyomavirus...
  11. doi request reprint Synthesis and significant cytostatic activity of 7-hetaryl-7-deazaadenosines
    Aurélie Bourderioux
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    J Med Chem 54:5498-507. 2011
    ..Initial in vivo evaluation demonstrated an effect of 7-(2-thienyl)-7-deazaadenine ribonucleoside on the survival rate in syngeneic P388D1 mouse leukemia model...
  12. doi request reprint 6-(Het)aryl-7-deazapurine ribonucleosides as novel potent cytostatic agents
    Petr Naus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam 2, CZ 16610 Prague 6, Czech Republic
    J Med Chem 53:460-70. 2010
    ..Intracellular phosphorylation to mono- and triphosphates and the inhibition of total RNA synthesis was demonstrated in preliminary study of metabolism and mechanism of action studies...
  13. pmc Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors
    Gabriel Birkus
    Gilead Sciences, Foster City, California 94404, USA
    Antimicrob Agents Chemother 46:716-23. 2002
    ..2 microM) and to achieve therapeutically relevant levels in plasma (maximum concentrations in plasma, 0.8 to 1.3 microM) is not associated with mitochondrial toxicity...
  14. doi request reprint Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides
    Pavla Perlíková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam 2, CZ 16610 Prague 6, Czech Republic
    Bioorg Med Chem 19:229-42. 2011
    ..More likely, active efflux of prodrugs may play a role in their weak cytotoxic activity...
  15. doi request reprint Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir
    Kirsten M Stray
    Gilead Sciences, Inc, Foster City, California, USA
    Antimicrob Agents Chemother 57:4982-9. 2013
    ..These results illustrate that COBI and TFV interact primarily with distinct renal transporters and indicate a low potential for pharmacokinetic renal drug-drug interaction. ..
  16. doi request reprint Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design
    Eric B Lansdon
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, California 94404, USA
    J Med Chem 53:4295-9. 2010
    ..Comparison to previously published structures reveals differences in binding modes for TMC125 and differences in protein conformation for TMC278...
  17. doi request reprint GS-9219--a novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin's lymphoma
    Hans Reiser
    Department of Research and Development, Gilead Sciences, Inc, Foster City, California 94404, USA
    Clin Cancer Res 14:2824-32. 2008
    ..Our objective was to characterize the antiproliferative activity, pharmacokinetics, pharmacodynamics, and safety of GS-9219...