FY20: PURPOSE TO AWARD TASK ORDER NO. 75N95020F00001 (RECEPTOR PROFILES) IDIQ CONTRACT NO. HHSN271201800024I FOR WORK AS DESCRIBED FOR NIDA CONTRACT T

根据任务1，承包商应收到最多四十五(45)个待评估的测试化合物，以进行受体特征筛选。承包商应以两种浓度(100纳米和10,000纳米)对这些化合物进行两次筛选(每个目标四(4)个井)。除非项目主管另有要求，承包商应筛选出对简档中所列生物目标的约束性。根据任务2，承包商应对受体结合、功能活性或其他分析进行最多六十(60)次评估。要进行的分析的确切数量和类型通常在任务1工作完成后才能确定，但可能包括受体、转运体和酶位点的结合和功能活性测量。每个评估应包括两个重复，每个重复中使用重复孔(每次分析共32个孔)，共八(8)个浓度，并将确定目标受体的IC50/KI或功能活性。在100和10,000 nm的两份(4孔)或NIDA COR规定的其他浓度下进行筛选试验，可在研究之前进行，以帮助确定待测试的最佳浓度范围)功能分析将包括激动剂和拮抗剂功能，除非NIDA COR另有规定。根据任务3，承包商应进行最多六十(60)项毒性检测，包括细胞色素P450图谱、HERG通道检测、Ames突变检测和P-gp底物检测。每个CYP450图谱应包括在100和10,000 nm处测试工作说明书中规定的六(6)种CYP450酶的重复孔(总共二十四(24)孔)。KI/IC50的评估将在每个位置进行，其中配置文件显示在任一浓度下至少有25%(25%)的结合抑制(HIT)。每一次后续评估应包括两次重复，每次重复使用重复孔(每次分析共32孔)，共八(8)个浓度。HERG通道分析将包括五(5)个浓度和三个细胞(总共15个数据点)。根据任务6，承包商应在NIDA核心的指导下购买最多五种化合物进行测试。NIDA COR之前已经确定，这些化合物不能在美国购买，并在合理的时间框架内运往承包商。

Under Task 1, the Contractor shall receive up to forty-five (45) 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 sixty (60) 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). Under Task 6, the Contractor shall purchase up to five 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.