Bictegravir is a potent, unboosted, once-Daily HIV-1 Integrase Strand Transfer inhibitor (INSTI) (IC50 - 1.6 nM) with improved pharmacokinetics and in vitro resistance profile.
Unique among animal viruses is the requirement for retroviruses to integrate their genetic information into the genome of the host cell that they infect. Integration is mediated by the viral protein integrase (IN), which is incorporated into fledgling viral particles alongside the other viral enzymes reverse transcriptase (RT) and protease (PR)[4]. Bictegravir (BIC), a novel, potent, once-daily, unboosted inhibitor of HIV-1 integrase (IN), specifically targets IN strand transfer activity with IC50 of 7.5 ± 0.3 nM and HIV-1 integration in cells[5]. BIC exhibits potent and selective in vitro antiretroviral activity in both T-cell lines and primary human T lymphocytes, with EC50s ranging from 1.5 to 2.4 nM and selectivity indices up to 8,700 relative to cytotoxicity. BIC displayed an in vitro resistance profile that was markedly improved compared to the integrase strand transfer inhibitors (INSTIs) raltegravir (RAL) and elvitegravir (EVG), and comparable to that of dolutegravir (DTG), against nine INSTI-resistant site-directed HIV-1 mutants. BIC displayed statistically improved antiviral activity relative to EVG, RAL, and DTG against a panel of 47 patient-derived HIV-1 isolates with high-level INSTI resistance. A high barrier to in vitro resistance emergence for BIC was also observed in viral breakthrough studies in the presence of constant clinically relevant drug concentrations[5].
Bictegravir 动物研究
Dose
Male Cynomolgus Monkey[3]: 0.5 mg/kg (i.v.); 1 mg/kg (p.o.)
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