Method and compositions for identifying anti-HIV therapeutic compounds

A method for identifying a candidate compound as a suitable pro-drug, comprising:

• (a) providing the candidate compound having an esterified phosphonate group or an esterified carboxyl group;
• (b) contacting the candidate compound with an extract of peripheral blood mononuclear cells having carboxylic ester hydrolase activity to produce a metabolite compound;
• and
• (c) identifying the candidate compound as a suitable pro-drug if the metabolite compound has a phosphonic acid group instead of the esterified phosphonate group of the candidate compound, or a carboxylic acid group instead of the esterified carboxyl group of the candidate compound.

A method for identifying a candidate compound as a suitable pro-drug, comprising:

• (a) providing the candidate compound having an esterified phosphonate group;
• (b) contacting the candidate compound with GS-7340 Ester Hydrolase to produce a metabolite compound;
• and
• (c) identifying the candidate compound as a suitable pro-drug if the metabolite compound has a phosphonic acid group instead of the esterified phosphonate group of the candidate compound.

A method for identifying a candidate compound as a suitable pro-drug, comprising:

• (a) providing the candidate compound having an esterified carboxyl group;
• (b) contacting the candidate compound with GS-7340 Ester Hydrolase to produce an metabolite compound;
• and
• (c) identifying the candidate compound as a suitable pro-drug if the metabolite compound has a carboxylic acid group instead of the esterified carboxyl group of the candidate compound.

A method for identifying a candidate compound as a suitable pro-drug, comprising:

• (a) providing the candidate compound having an esterified phosphonate group or an esterified carboxyl group;
• (b) contacting the candidate compound with an extract of peripheral blood mononuclear cells which has carboxylic ester hydrolase activity but does not cleave alpha-napthyl acetate, to produce a metabolite compound;
• and
• (c) identifying the candidate compound as a suitable pro-drug if the metabolite compound has a phosphonic acid group instead of the esterified phosphonate group of the candidate compound, or a carboxylic acid group instead of the esterified carboxyl group of the candidate compound.