FY20. RECEPTOR PROFILES - TASK ORDER NO. 75N95020F00159 POP: SEPTEMBER 30, 2020 - SEPTEMBER 29, 2021. N01DA-18-8937.

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Under Task 1, the Contractor shall receive up to twenty-nine (29) test compounds to be evaluated for receptor profile screening. The Contractor shall screen these compounds at two concentrations (100 nM and 10,000 nM) in duplicate (four (4) wells per target). The Contractor shall screen for binding at the biological targets listed in the profile unless otherwise requested by the Project Officer. Under Task 2, the Contractor shall perform up to eighty (80) evaluations of receptor binding, functional activity, or other assays. The exact number and type of assays to be performed usually cannot be specified until after Task 1 work is completed but may include both binding and functional activity measures at receptor, transporter, and enzyme sites. Each evaluation shall consist of two replications of eight (8) concentrations using duplicate wells in each replication (total of 32 wells per assay) and will determine the IC50/Ki or functional activity at the target receptor. A screening assay at 100 and 10,000 nM in duplicate (4 wells) or other concentrations as specified by the NIDA COR may be performed prior to study to help determine the best range of concentrations to be tested. Functional assays will include both agonist and antagonist function unless otherwise specified by the NIDA COR. Under Task 3, the Contractor shall perform up to sixty (60) toxicity assays including Cytochrome P450 profiles, hERG channel assays, Ames mutagenicity assays and P-gp substrate assays. Each Cyp450 profile shall consist of testing duplicate wells at 100 and 10,000 nM for six (6) Cyp450 enzymes specified in the Statement of Work (total of twenty-four (24) wells). A Ki/IC50 evaluation will be performed at each site where the profile shows at least twenty-five percent (25%) binding inhibition at either concentration (a “hit”). Each follow-up evaluation shall consist of two replications of eight (8) concentrations using duplicate wells in each replication (total of 32 wells per assay). The hERG channel assay will consist of five (5) concentrations and triplicate cells (total of 15 data points). The micronucleus assay will consist of 8 concentrations tested in triplicate wells with and without exposure to S9 (48 wells total) unless otherwise directed by the NIDA COR. Under Task 6, the Contractor shall purchase up to five (5) compounds for testing at the direction of the NIDA COR. The NIDA COR will have determined previously that the compounds could not be purchased in the United States and shipped to the Contractor in a reasonable time frame. Money to be used for this Task will be subtracted from the amount of money allocated to other Tasks and the number of assays performed under such Tasks reduced.