J. P. Kleim

Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype (2001)

Schmit, J C, Esnouf, R, ...

OBJECTIVES: To investigate the genotypic and phenotypic effects of in vitro resistance selection with lamivudine and/or the second generation non-nucleoside reverse transcriptase inhibitor (NNRTI)...

Rational Dose Selection for a Nonnucleoside Reverse Transcriptase Inhibitor through Use of Population Pharmacokinetic Modeling and (2001)

Monte Carlo Simulation, G. L. Drusano, J. P. Kleim, W. Prince, A. Bye

In order to choose a rational dose for GW 420867X, we first set a goal of therapy. We hypothesized that, for optimal antiretroviral activity, the trough free drug concentration should remain above...

Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors (2000)

Burt, V, Kleim, J P

The novel quinoxaline GW420867X has been combined with a variety of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in...

Retention of marked sensitivity to (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-di hydroquin oxaline-2(1H)-thione (HBY 097) by an azidothymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) strain subcultured in the combined presence of quinoxaline HBY 097 and 2',3'-dideoxy-3'-thiacytidine (lamivudine) (1998)

Riess, G, Roesner, M, Winkler, I, ...

An azidothymidine (AZT)-resistant virus strain (HIV-1/AZT) (containing the 67 Asp --> Asn, 70 Lys --> Arg, 215 Thr --> Phe and 219 Lys --> Gln mutations into its reverse transcriptase) was grown in...

Zidovudine-resistant human immunodeficiency virus type 1 strains subcultured in the presence of both lamivudine and quinoxaline HBY 097 retain marked sensitivity to HBY 097 but not to lamivudine (1997)

Riess, G, Roesner, M, Winkler, I, ...

Replication of zidovudine-resistant human immunodeficiency virus type 1 (HIV-1) strains (containing the 41 Met-->Leu and 215 Thr-->Tyr mutations in reverse transcriptase [RT]) was inhibited to a...

Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1 (1997)

Esnouf, R, Dunkler, A, Parniak, M A, Karlsson, A, ...

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected CEM cell cultures with escalating concentrations of the quinoxaline S-2720 resulted in an ordered appearance of single and multiple...

Reverse transcriptase fidelity and HIV-1 variation (1997)

Karlsson, A, Kleim, J P

Concomitant combination therapy for HIV infection preferable over sequential therapy with 3TC and non-nucleoside reverse transcriptase inhibitors (1996)

Karlsson, A, Kleim, J P

Exposure to 3TC of HIV-1 mutant strains containing non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific mutations in their reverse transcriptase (RT) easily selected for double-mutant...

Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720 (1994)

Karlsson, A, Meichsner, C, Paessens, A, Riess, G, ...

The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1-induced cytopathicity in CEM cells...

Sensitivity of (138 Glu-->Lys) mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors (1994)

Kleim, J P, Riess, G, Camarasa, M J, Karlsson, A

Human immunodeficiency virus type 1 (HIV-1) recombinant reverse transcriptase (RT) containing lysine (Lys) instead of glutamic acid (Glu) at position 138 proved fully resistant to the inhibitory...

Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants.

Kleim, J P, Rösner, M, Winkler, I, Paessens, A, Kirsch, R, Hsiou, Y, ...

The quinoxaline nonnucleoside RT inhibitor (NNRTI) (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4- dihydroquinoxaline-2(1H)-thione (HBY 097) was used to select for drug-resistant HIV-1...

Rational Dose Selection for a Nonnucleoside Reverse Transcriptase Inhibitor through Use of Population Pharmacokinetic Modeling and Monte Carlo Simulation

Drusano, G. L., Moore, K. H. P., Kleim, J. P., Prince, W., Bye, A.

In order to choose a rational dose for GW 420867X, we first set a goal of therapy. We hypothesized that, for optimal antiretroviral activity, the trough free drug concentration should remain above...

Preclinical evaluation of HBY 097, a new nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 replication.

Kleim, J P, Bender, R, Kirsch, R, Meichsner, C, Paessens, A, Rösner, M, ...

HBY 097 [(S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroquinoxaline-2(1H)-thione] was selected from a series of quinoxalines as a nonnucleoside inhibitor of human...

Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication.

Kleim, J P, Bender, R, Billhardt, U M, Meichsner, C, Riess, G, Rösner, M, ...

S-2720 [6-chloro-3,3-dimethyl-4-(isopropenyloxycarbonyl)-3,4- dihydroquinoxalin-2(1H)-thione], a quinoxaline derivative, was found to be a very potent inhibitor of both human immunodeficiency virus...

Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1.

Pelemans, H, Esnouf, R, Dunkler, A, Parniak, M A, Vandamme, A M, Karlsson, A, ...

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected CEM cell cultures with escalating concentrations of the quinoxaline S-2720 resulted in an ordered appearance of single and multiple...

Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720.

Balzarini, J, Karlsson, A, Meichsner, C, Paessens, A, Riess, G, De Clercq, E, ...

The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1-induced cytopathicity in CEM cells...

Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants.

Kleim, J P, Rösner, M, Winkler, I, Paessens, A, Kirsch, R, Hsiou, Y, ...

The quinoxaline nonnucleoside RT inhibitor (NNRTI) (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4- dihydroquinoxaline-2(1H)-thione (HBY 097) was used to select for drug-resistant HIV-1...

Rational Dose Selection for a Nonnucleoside Reverse Transcriptase Inhibitor through Use of Population Pharmacokinetic Modeling and Monte Carlo Simulation

Drusano, G. L., Moore, K. H. P., Kleim, J. P., Prince, W., Bye, A.

In order to choose a rational dose for GW 420867X, we first set a goal of therapy. We hypothesized that, for optimal antiretroviral activity, the trough free drug concentration should remain above...

Preclinical evaluation of HBY 097, a new nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 replication.

Kleim, J P, Bender, R, Kirsch, R, Meichsner, C, Paessens, A, Rösner, M, ...

HBY 097 [(S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroquinoxaline-2(1H)-thione] was selected from a series of quinoxalines as a nonnucleoside inhibitor of human...

Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication.

Kleim, J P, Bender, R, Billhardt, U M, Meichsner, C, Riess, G, Rösner, M, ...

S-2720 [6-chloro-3,3-dimethyl-4-(isopropenyloxycarbonyl)-3,4- dihydroquinoxalin-2(1H)-thione], a quinoxaline derivative, was found to be a very potent inhibitor of both human immunodeficiency virus...

Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1.

Pelemans, H, Esnouf, R, Dunkler, A, Parniak, M A, Vandamme, A M, Karlsson, A, ...

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected CEM cell cultures with escalating concentrations of the quinoxaline S-2720 resulted in an ordered appearance of single and multiple...

Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720.

Balzarini, J, Karlsson, A, Meichsner, C, Paessens, A, Riess, G, De Clercq, E, ...

The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1-induced cytopathicity in CEM cells...