Cobicistat

Cobicistat is a potent and selective inhibitor of cytochrome P450 3A (CYP3A) enzymes with IC₅₀s of 30-285 nM. Cobicistat is a pharmacokinetic enhancer which increases the overall absorption of several HIV medications. IC50 & Target:IC50: 30-285 nM (Cytochrome P450)^[1] In Vitro:In HIV-1 protease enzymatic assay and antiviral cellular assays. Cobicistat is inactive against HIV-1 protease (IC₅₀>30 μM) . And Cobicistat has no inhibitory effect against HIV replication in a multicycle 5-day MT-2 HIV infection assay (EC₅₀>30 μM). In assays using MT-2 cells, Cobicistat exhibits minimal cytotoxicity, with a CC₅₀ value above 80 μM^[1].
The mode of inhibition of human CYP3A by Cobicistat and Ritonavir shares the same mechanism of action for the inhibition of CYP3A. It shows its inhibitory effects on CYP3A may involve directly at the heme group of the CYP3A enzyme^[1].
The minimal adverse effects of Cobicistat in these assays suggest a lower potential for toxicity related to altered lipid metabolism.
In the lipid accumulation assay with the human adipocytes, Ritonavir shows a clear effect with an EC₅₀ of 16 μM. However, Cobicistat exhibits no effect at a concentration up to 30 μM^[1].
In the glucose uptake assay with mouse adipocytes, Ritonavir shows a pronounced effect at the concentration of 10 μM. In contrast, the effects on glucose uptake by Cobicistat (10 μM) is significantly less^[1].