Journal: ACS Omega

Article Title: Structure–Activity Relationship Studies of Emtricitabine Prodrugs toward Long-Acting Antiretroviral Formulations

doi: 10.1021/acsomega.5c03319

Figure Lengend Snippet: Representative data showing hydrolysis of prodrug 4 in the liver (2 mg/mL) and muscle S9 fractions, and plasma. (a) Scheme showing the expected hydrolysis reaction. Representative HPLC stack plots (305 nm, λ max of FTC carbamates) and calculated initial rate of hydrolysis of 4 to 3 are shown for (b) human liver S9, (c) human muscle S9, and (d) human plasma.

Article Snippet: Reaction mixtures (95 μL) containing phosphate buffer (0.1 M, pH 7.4) and pooled, mixed gender liver S9 (Xenotech) (5.0 mg/mL: 17 ) (2.0 mg/mL: 4 – 10, 12, 14 – 16 , 18 – 20 ) (1.0 mg/mL: 13 ) were preincubated in 1.5 mL microcentrifuge tubes at 37 °C for 5 min. Prodrug stocks (20 mM) in DMSO were prepared at room temperature.

Techniques: Clinical Proteomics

Journal: ACS Omega

Article Title: Structure–Activity Relationship Studies of Emtricitabine Prodrugs toward Long-Acting Antiretroviral Formulations

doi: 10.1021/acsomega.5c03319

Figure Lengend Snippet: Effect of the 5′-carbonate chain length on the rate of prodrug hydrolysis under physiological conditions. (a) Reaction of 5′-carbonate FTC carbamates 4 – 11 to form 3 in human liver S9, (b) human muscle S9, and (c) human plasma. Initial rates of 5′-carbonate hydrolysis are shown. Error represents the standard deviation, n = 3. a Relative to 11 ; b This prodrug conversion rate was previously reported in ref .

Article Snippet: Reaction mixtures (95 μL) containing phosphate buffer (0.1 M, pH 7.4) and pooled, mixed gender liver S9 (Xenotech) (5.0 mg/mL: 17 ) (2.0 mg/mL: 4 – 10, 12, 14 – 16 , 18 – 20 ) (1.0 mg/mL: 13 ) were preincubated in 1.5 mL microcentrifuge tubes at 37 °C for 5 min. Prodrug stocks (20 mM) in DMSO were prepared at room temperature.

Techniques: Clinical Proteomics, Standard Deviation

Journal: ACS Omega

Article Title: Structure–Activity Relationship Studies of Emtricitabine Prodrugs toward Long-Acting Antiretroviral Formulations

doi: 10.1021/acsomega.5c03319

Figure Lengend Snippet: Hydrolysis rates of 5′ esters. In vitro metabolism of prodrugs 11 – 20 under physiological conditions. (a) Summary of prodrug hydrolysis. Error represents the standard deviation, n = 3. a Relative to 11 ; b this prodrug conversion rate was previously reported in ref . c Only FTC was observed. d No ester hydrolysis was observed under assay conditions. e Not attempted. ND = not determined, n = 3. (b) Prodrug 13 is completely hydrolyzed in liver S9 fraction (2 mg/mL liver) within 10 min.

Article Snippet: Reaction mixtures (95 μL) containing phosphate buffer (0.1 M, pH 7.4) and pooled, mixed gender liver S9 (Xenotech) (5.0 mg/mL: 17 ) (2.0 mg/mL: 4 – 10, 12, 14 – 16 , 18 – 20 ) (1.0 mg/mL: 13 ) were preincubated in 1.5 mL microcentrifuge tubes at 37 °C for 5 min. Prodrug stocks (20 mM) in DMSO were prepared at room temperature.

Techniques: In Vitro, Standard Deviation