Cabotegravir (GSK-1265744) operates as an orally available, long-acting inhibitor of the HIV integrase strand transfer and the organic anion transporters 1 and 3 (OAT1/OAT3), with IC50s of 2.5 nM for HIVADA, 0.41 μM for OAT3, and 0.81 μM for OAT1. Its metabolism is mainly via the uridine diphosphate glucuronosyltransferase (UGT) 1A1, presenting minimal interaction risks with other antiretroviral drugs (ARVs), making it suitable for AIDS researc[1].[2].
体内研究
Cabotegravir administered intravenously at doses of either 25 or 50 mg/kg, once or twice, effectively shields Macaques from an intravenous SIVmac251 challenge[4].
体外研究
Cabotegravir (GSK-1265744) inhibits the HIV-1 integrase catalyzed strand transfer reaction with an IC50 of 3.0 nM in vitro.It shows antiviral activity with EC50 values ranging from 0.22 nM to 1.3 nM against various HIV-1 strains in different cellular assays. Additionally, it effectively shields Macaques from intravenous SIVmac251 challenges when administered as a single or double dose of 25 or 50 mg/kg intravenously[3].
Cabotegravir/卡博特韦 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CEMss cells
0.14 to 1.3 nM
6 days
Assess the antiviral activity of Cabotegravir against HIV-2 in a spreading infection model, demonstrating high efficacy.
To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines.
Int J Mol Sci. 2024 Jan 28;25(3):1615.
FO-1
0.5 µM and 3 µM
72 hours
To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines.
Int J Mol Sci. 2024 Jan 28;25(3):1615.
SK-Mel-28
0.5 µM and 3 µM
72 hours
To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines.
Int J Mol Sci. 2024 Jan 28;25(3):1615.
A375
0.5 µM and 3 µM
72 hours
To evaluate the effect of Cabotegravir on melanoma cell viability, results showed that Cabotegravir exhibited the greatest capability to diminish cell viability across all four melanoma cell lines.
Int J Mol Sci. 2024 Jan 28;25(3):1615.
MAGIC-5A cells
1.2 to 1.7 nM (EC50)
Evaluate the antiviral activity of Cabotegravir against HIV-1 and HIV-2, showing high efficacy against both viruses.
To determine the dose that would yield plasma drug concentrations similar to those observed in humans. Results showed that a 10× dose (5 mg/kg/day) of Cabotegravir resulted in a Cmax concentration of ~3500 ng/mL and a Cmin of ~1300 ng/mL, which are similar to those published in human pharmacokinetic studies.
Pharmaceutics. 2022 Aug 24;14(9):1761
Zebrafish
Zebrafish embryos
Immersion method
10-500 μM
From gastrula stage (4 hpf) up to 120 or 144 hpf
To assess the effects of Cabotegravir on zebrafish embryo development, including survival rate, morphological assessments, hatching rate, and neurotoxicity. Results showed that CAB at the highest concentrations caused pericardial edema, uninflated swim bladder, decreased heartbeats, growth delay, and decreased hatching rate. Decreased locomotion was observed even at the subtherapeutic dose, suggesting alterations of nervous system integrity.
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