Next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors.
This review discusses the desired attributes of a next-generation HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) and highlights the properties of compounds currently or recently in clinical development. TMC-125 is currently in phase III clinical trials and on track to become the first NNRTI suitable for use in NNRTI-experienced patients. TMC-278 is structurally related to TMC-125, but is more potent in vitro and has pharmacokinetics suitable for once-daily administration. It is currently undergoing phase II clinical trials. BILR-355 BS, a dipyridodiazepinone compound, is in early phase II clinical trials. It requires ritonavir as a booster and has reduced inhibitory activity against several key NNRTI-resistant HIV-1 strains. Development of the NNRTIs capravirine and GW-695634 has been discontinued because of lack of efficacy and safety issues, respectively.
Boone
Lawrence R
LR
GlaxoSmithKline, Discovery Virology, Research Triangle Park, NC 27709, USA. larry.r.boone@gsk.com
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000068696:Rilpivirine
D019380:Anti-HIV Agents; D001381:Azepines; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine