T Cihlar

Summary

Affiliation: Gilead Sciences
Country: USA

Publications

  1. ncbi request reprint The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1
    T Cihlar
    Gilead Sciences, Foster City, California, USA
    Mol Pharmacol 56:570-80. 1999
  2. 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
  3. ncbi request reprint Expression of the catalytic subunit (UL54) and the accessory protein (UL44) of human cytomegalovirus DNA polymerase in a coupled in vitro transcription/translation system
    T Cihlar
    Gilead Sciences, 333 Lakeside Drive, Foster City, California 94404, USA
    Protein Expr Purif 11:209-18. 1997
  4. pmc Characterization of drug resistance-associated mutations in the human cytomegalovirus DNA polymerase gene by using recombinant mutant viruses generated from overlapping DNA fragments
    T Cihlar
    Gilead Sciences, Foster City, California 94404, USA
    J Virol 72:5927-36. 1998
  5. ncbi request reprint A point mutation in the human cytomegalovirus DNA polymerase gene selected in vitro by cidofovir confers a slow replication phenotype in cell culture
    T Cihlar
    Gilead Sciences, 333 Lakeside Drive, Foster City, California, 94404, USA
    Virology 248:382-93. 1998
  6. ncbi request reprint Fluorescence-based assay for the interaction of small molecules with the human renal organic anion transporter 1
    T Cihlar
    Gilead Sciences, Foster City, California 94404, USA
    Anal Biochem 283:49-55. 2000
  7. pmc Conversion of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine to cidofovir by an intracellular cyclic CMP phosphodiesterase
    D B Mendel
    Gilead Sciences, Inc, Foster City, California 94404, USA
    Antimicrob Agents Chemother 41:641-6. 1997
  8. ncbi request reprint Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity
    M D Miller
    Gilead Sciences, Foster City, California 94404, USA
    Mol Pharmacol 54:291-7. 1998
  9. ncbi request reprint Comparative effects of adefovir and selected nucleoside inhibitors of hepatitis B virus DNA polymerase on mitochondrial DNA in liver and skeletal muscle cells
    G Birkus
    Gilead Sciences, Foster City, CA 94404, USA
    J Viral Hepat 10:50-4. 2003
  10. ncbi request reprint Expression and characterization of soluble human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein
    Z M Wang
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    J Virol Methods 98:53-61. 2001

Collaborators

Detail Information

Publications32

  1. ncbi request reprint The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1
    T Cihlar
    Gilead Sciences, Foster City, California, USA
    Mol Pharmacol 56:570-80. 1999
    ....
  2. 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...
  3. ncbi request reprint Expression of the catalytic subunit (UL54) and the accessory protein (UL44) of human cytomegalovirus DNA polymerase in a coupled in vitro transcription/translation system
    T Cihlar
    Gilead Sciences, 333 Lakeside Drive, Foster City, California 94404, USA
    Protein Expr Purif 11:209-18. 1997
    ..This straightforward method for protein expression may also be applicable to other enzymes where reproducible generation of fully functional products is desirable...
  4. pmc Characterization of drug resistance-associated mutations in the human cytomegalovirus DNA polymerase gene by using recombinant mutant viruses generated from overlapping DNA fragments
    T Cihlar
    Gilead Sciences, Foster City, California 94404, USA
    J Virol 72:5927-36. 1998
    ..Results of this work exemplify specific roles of the UL54 conserved regions in the development of HCMV drug resistance and may help guide optimization of HCMV therapy...
  5. ncbi request reprint A point mutation in the human cytomegalovirus DNA polymerase gene selected in vitro by cidofovir confers a slow replication phenotype in cell culture
    T Cihlar
    Gilead Sciences, 333 Lakeside Drive, Foster City, California, 94404, USA
    Virology 248:382-93. 1998
    ....
  6. ncbi request reprint Fluorescence-based assay for the interaction of small molecules with the human renal organic anion transporter 1
    T Cihlar
    Gilead Sciences, Foster City, California 94404, USA
    Anal Biochem 283:49-55. 2000
    ....
  7. pmc Conversion of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine to cidofovir by an intracellular cyclic CMP phosphodiesterase
    D B Mendel
    Gilead Sciences, Inc, Foster City, California 94404, USA
    Antimicrob Agents Chemother 41:641-6. 1997
    ..Importantly, hydrolysis of cHPMPC is not diminished in cells infected with HCMV...
  8. ncbi request reprint Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity
    M D Miller
    Gilead Sciences, Foster City, California 94404, USA
    Mol Pharmacol 54:291-7. 1998
    ..These results with recombinant K70E RT are consistent with the reduced in vitro replication capacity of the K70E RT mutant of HIV-1 and further demonstrate that the K70E mutation confers minor PMEA and 3TC resistance to HIV-1...
  9. ncbi request reprint Comparative effects of adefovir and selected nucleoside inhibitors of hepatitis B virus DNA polymerase on mitochondrial DNA in liver and skeletal muscle cells
    G Birkus
    Gilead Sciences, Foster City, CA 94404, USA
    J Viral Hepat 10:50-4. 2003
    ..The effects of FIAU on mtDNA became more pronounced following prolonged 18-day treatment of skeletal muscle cells while the effects of other drugs remained unchanged...
  10. ncbi request reprint Expression and characterization of soluble human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein
    Z M Wang
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    J Virol Methods 98:53-61. 2001
    ..The establishment of this expression and purification system has allowed us to further explore the biochemical characteristics of paramyxovirus HN and to obtain material that could be suitable for X-ray crystallography studies...
  11. ncbi request reprint Synthesis, anti-HIV activity, and resistance profile of thymidine phosphonomethoxy nucleosides and their bis-isopropyloxymethylcarbonyl (bisPOC) prodrugs
    Richard L Mackman
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Bioorg Med Chem 15:5519-28. 2007
    ....
  12. ncbi request reprint Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates
    Richard L Mackman
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Bioorg Med Chem Lett 17:6785-9. 2007
    ..1 microM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT...
  13. pmc Intracellular metabolism of the nucleotide prodrug GS-9131, a potent anti-human immunodeficiency virus agent
    Adrian S Ray
    Department of Drug Metabolism, Gilead Sciences, Inc, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 52:648-54. 2008
    ..Together, these observations elucidate the cellular pharmacology of GS-9131 and illustrate its efficient loading of lymphoid cells, resulting in a prolonged intracellular exposure to the active metabolite GS-9148-DP...
  14. pmc Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131
    Tomas Cihlar
    Gilead Sciences, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 52:655-65. 2008
    ..This favorable preclinical profile makes GS-9131 an attractive clinical development candidate for the treatment of patients infected with NRTI-resistant HIV...
  15. ncbi request reprint Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: a comparison of phosphonates and corresponding nucleosides
    Richard L Mackman
    Gilead Sciences, Inc, Foster City, California 94404, USA
    Nucleosides Nucleotides Nucleic Acids 26:573-7. 2007
    ..Bis-isopropyloxymethylcarbonyl (BisPOC) prodrugs were prepared on selected compounds and provided > 150-fold improvements in antiviral activity...
  16. ncbi request reprint Synthesis and anti-HIV activity of 2'-fluorine modified nucleoside phosphonates: analogs of GS-9148
    Richard L Mackman
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Bioorg Med Chem Lett 18:1116-9. 2008
    ..The antiviral activity of guanosine analog (2'-Fd4GP) was comparable that of to 2'-Fd4AP in MT-2 cells, but selectivity was reduced...
  17. doi request reprint Synthesis and anti-HIV activity of GS-9148 (2'-Fd4AP), a novel nucleoside phosphonate HIV reverse transcriptase inhibitor
    Constantine G Boojamra
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Bioorg Med Chem Lett 18:1120-3. 2008
    ....
  18. 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
    ....
  19. 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...
  20. ncbi request reprint Molecular assessment of the potential for renal drug interactions between tenofovir and HIV protease inhibitors
    Tomas Cihlar
    Gilead Sciences, Foster City, CA, USA
    Antivir Ther 12:267-72. 2007
    ....
  21. ncbi request reprint Unlikely association of multidrug-resistance protein 2 single-nucleotide polymorphisms with tenofovir-induced renal adverse events
    Adrian S Ray
    J Infect Dis 195:1389-90; author reply 1390-1. 2007
  22. 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...
  23. ncbi request reprint The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies
    George Hill
    Roche Pharmaceutical Global Development, 3401 Hillview Avenue, Palo Alto, CA 94304, USA
    Drug Metab Dispos 30:13-9. 2002
    ..The study results demonstrate that oseltamivir has a low drug-drug interaction potential at the renal tubular level due to inhibition of hOAT1...
  24. 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...
  25. pmc Inhibition of respiratory syncytial virus fusion by the small molecule VP-14637 via specific interactions with F protein
    Janet L Douglas
    Gilead, Foster City, California 94404, USA
    J Virol 77:5054-64. 2003
    ..Therefore, we propose that VP-14637 inhibits RSV through a novel mechanism involving an interaction between the compound and a transient conformation of the RSV F protein...
  26. ncbi request reprint Inhibition of the human organic anion transporter 1 by the caffeine metabolite 1-methylxanthine
    Jens Rengelshausen
    Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Biochem Biophys Res Commun 320:90-4. 2004
    ..The central involvement of hOAT1 in the renal excretion of numerous drugs suggests that this inhibition may alter the pharmacokinetics of a series of clinically important drugs in humans...
  27. pmc Selective intracellular activation of a novel prodrug of the human immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to preferential distribution and accumulation in lymphatic tissue
    William A Lee
    Gilead Sciences, Inc, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 49:1898-906. 2005
    ..2 microg-eq/ml in plasma. A radiolabeled distribution study with dogs resulted in an increased distribution of tenofovir to tissues of lymphatic origin compared to the commercially available prodrug tenofovir DF (Viread)...
  28. pmc Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms
    Janet L Douglas
    Gilead, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 49:2460-6. 2005
    ..Altogether, these data indicate that VP-14637 and JNJ-2408068 interfere with RSV fusion through a mechanism involving a similar interaction with the F protein...
  29. pmc In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells
    Francesc Vidal
    Infectious Diseases and AIDS Section, Department of Internal Medicine, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, Mallafre Guasch, 4, 43007 Tarragona, Spain
    Antimicrob Agents Chemother 50:3824-32. 2006
    ..Together, these in vitro results indicate that combination with other antiretrovirals does not significantly increase the toxic potential of TFV in RPTECs...
  30. ncbi request reprint Suppression of HIV-1 protease inhibitor resistance by phosphonate-mediated solvent anchoring
    Tomas Cihlar
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    J Mol Biol 363:635-47. 2006
    ..This strategy, which is applicable to various PI scaffolds, should facilitate the design of novel PIs and potentially other antiviral therapeutics...
  31. pmc Mechanism of active renal tubular efflux of tenofovir
    Adrian S Ray
    Department of Drug Metabolism, Gilead Sciences, Inc, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 50:3297-304. 2006
    ..A detailed understanding of the molecular mechanism of TFV active tubular secretion will facilitate the assessment of potential renal drug-drug interactions with coadministered agents...
  32. pmc Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects
    Koen K A Van Rompay
    California National Primate Research Center, University of California, Davis, California 95616, USA
    Antimicrob Agents Chemother 52:3144-60. 2008
    ..In conclusion, these findings illustrate the safety and sustained benefits of prolonged TFV-containing regimens throughout development from infancy to adulthood, including pregnancy...