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. 2017 Mar;66(3):660-661.
doi: 10.1016/j.jhep.2016.11.025. Epub 2016 Dec 10.

Covalent inhibition of carboxylesterase-2 by sofosbuvir and its effect on the hydrolytic activation of tenofovir disoproxil

Yuanjun Shen  1 , Bingfang Yan  2
Affiliations

Covalent inhibition of carboxylesterase-2 by sofosbuvir and its effect on the hydrolytic activation of tenofovir disoproxil

Yuanjun Shen et al. J Hepatol. 2017 Mar.
No abstract available

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Conflict of interest statement

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Figures

Fig. 1.
Fig. 1.. Inhibition of CES2 by sofosbuvir.
(A) Inhibition of microsomal hydrolysis by sofosbuvir microsomes for human liver (0.25 μg/per well) or kidney (1 μg/per well) were incubated with sofosbuvir for 120 min at 0–50 μM in a total volume of 90 μl and then 10 μl of p-nitrophenylacetate (PNPA) was added at a final concentration of 1 mM. The hydrolysis of PNPA was monitored with a microplate-reader from an increase in the absorbance at 400 nm. (B) Native-gel electrophoresis stained for hydrolytic activity microsomes (0.25 μg) were incubated with sofosbuvir at 0–10 μM and subjected to native gel electrophoresis and stained for esterase activity with 4-methylumbelliferylacetate. (C) Inhibited hydrolysis of tenofovir disoproxil fumarate lysates from CES2 transfected cells were pre-incubated with sofosbuvir at 20 μM or the reaction buffer at 37 °C for 120 min, followed by addition of tenofovir disoproxil fumarate at a final concentration of 20 μM. The incubations lasted for an additional 30 min and were then mixed with acetonitrile at a final concentration of 66%. The reactions were centrifuged to remove the proteins and the supernatants were analyzed by high-performance liquid chromatography (Hitachi-300). (This figure appears in colour on the web.)
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