product name Cobicistat (GS-9350)
Description: Cobicistat (also known as GS-9350) is a potent and selective inhibitor of CYP3A with IC50 of 30-285 nM. Cobicistat is an FDA approved drug for the treatment of infection with the human immunodeficiency virus (HIV). Like ritonavir (Norvir), cobicistat is of interest not for its anti-HIV properties, but rather its ability to inhibit liver (CYP) enzymes that metabolize other medications used to treat HIV, notably elvitegravir, an HIV integrase inhibitor currently under investigation itself.
References: ACS Med. Chem. Lett, 2010, 1(5), 209-213.
776.02
Formula
C40H53N7O5S2
CAS No.
1004316-88-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (128.9 mM)
Water: <1 mg/mL
Ethanol: 100 mg/mL (128.9 mM)
Solubility (In vivo)
5% DMSO+40% PEG 300+ddH2O: 30mg/mL
Synonyms
GS9350
other peoduct :
| In Vitro |
In vitro activity: Cobicistat (GS-9350) is a potent, and selective inhibitor of human cytochrome P450 3A (CYP3A) enzymes as a pharmacoenhancer. GS-9350 inhibits CYP3A with IC50 spectrum from 30 nM to 285 nM. In contrast to ritonavir, GS-9350 is devoid of anti-HIV activity, with IC50 of > 30μM against HIV-1 protease and EC50 of > 30μM in MT-2 HIV infection assay, and is thus more suitable for use in boosting anti-HIV drugs without risking selection of potential drug-resistant HIV variants. GS-9350 shows reduced liability for drug interactions and may have potential improvements in tolerability over ritonavir. Kinase Assay: Inhibition of human cytochrome P450 activities is determined in duplicate in pooled human hepatic microsomal fractions following current scientific and regulatory guidelines. Reaction conditions are linear with respect to incubation time and hepatic microsomal protein concentration. Substrates are present at concentrations equal to or less than their respective Km values determined under the same reaction conditions. Metabolite and/or substrate concentrations are determined using specific, internal standard controlled HPLC MS/MS assays. For reactions monitoring metabolite formation there is less than 20% consumption of substrate during the reaction. Unless otherwise noted microsomal fraction, diluted in potassium phosphate buffer, is preincubated with substrate and inhibitor for 5 min at 37 ℃ and the reaction initiated by the addition of an NADPH generating system followed by further incubation at 37 ℃ with shaking. Enzyme-selective positive control inhibitors are tested in parallel. At appropriate times aliquots of the mixture are removed and the reaction terminated by addition to a mixture of methanol and acetonitrile containing the respective internal standard. After centrifugation aliquots of the supernatant are subjected to HPLC-MS/MS analysis. Cell Assay: |
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| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | ACS Med. Chem. Lett, 2010, 1(5), 209-213. |
