Published in Biochemical and Biophysical Research Communications
We reported that several HIV protease inhibitors (HIV-PIs) interfere with the endoproteolytic processing of two farnesylated proteins, yeast a-factor and mammalian prelamin A. We proposed that these drugs interfere with prelamin A processing by blocking ZMPSTE24, an integral membrane zinc metalloproteinase known to play a critical role in its proce...
Published in HIV/AIDS (Auckland, N.Z.)
There is an ongoing need for potent antiretroviral therapies to deal with the increasing pool of treatment-experienced patients with multiple drug resistance. The last few years have seen the arrival of 2 new and very potent protease inhibitors - darunavir and tipranavir - alongside 2 whole new classes of anti-HIV agents - the integrase inhibitors ...
Published in HIV/AIDS (Auckland, N.Z.)
Darunavir (formerly TMC114) is a second-generation, sulfonamide-based, peptidomimetic protease inhibitor (PI) with a modified 3-dimensional structure enabling more efficient binding to HIV protease. It has become an important drug, in combination with low-dose ritonavir boosting, in the treatment of both antiretroviral-naïve and multiclass-experien...
Published in Viruses
Antiviral inhibitors of HIV-1 protease are a notable success of structure-based drug design and have dramatically improved AIDS therapy. Analysis of the structures and activities of drug resistant protease variants has revealed novel molecular mechanisms of drug resistance and guided the design of tight-binding inhibitors for resistant variants. Th...
Published in European Journal of Medical Research
Multiclass-drug resistance, often caused by poor treatment compliance, is a challenging problem in all categories of HIV-infected patients. Selective pressure is higher in youth for both biological and behavioral reasons. We report the case of a 15-year-old Caucasian male, with vertically acquired HIV-1 infection, who failed several lines of antire...
Published in Therapeutics and clinical risk management
Darunavir is currently the most recently approved HIV-1 protease inhibitor. It is approved for twice-daily dosing with ritonavir in treatment-experienced patients as young as 6 years of age and is available in numerous pill strengths. Emergence of darunavir-specific mutations is generally slow; therefore it can retain activity against viral strains...
10.1371/journal.pone.0009643 / PLoS ONE / 5 / 3 / e9643
Published in Adolescent health, medicine and therapeutics
The introduction of protease inhibitors (PI) containing antiretroviral regimens in the treatment of HIV infection in infants, children, and adolescents has dramatically decreased morbidity and mortality. Darunavir, the latest PI to be FDA approved for pediatric patients older than 6 years and currently the preferred PI for use in adult patients, wa...
Published in ACS medicinal chemistry letters
A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand have been synthesized and evaluated. High affinity protease inhibitors (PIs) with an interesting activity on wild-type HIV and a panel of multi-PI resistant HIV-1 mutants containing clinically observed, primary mutations were identified using a cell-based assay. A num...
Ergänzend zu den in den letzten 7 Jahren publizierten Arzneimittelmonographien der Arbeitsgruppe Medikamente der Schweizerischen Gesellschaft für Klinische Chemie (SGKC) [1–6], sind weitere Monographien erstellt worden. Wiederum sollen diese Monographien dem Labormediziner bzw. dem Empfänger der Befunde eine Übersicht über die wichtigsten Informati...
