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

2020 财年：授予任务订单号的目的

• 批准号: 10286865
• 负责人: ANTHONY GALLACHER
• 金额: $ 30.96万
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-03 至 2021-04-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10286865
• 关键词: Agonist; Award; Binding; Biological; Biological Assay; Cells; Contractor; Contracts; Cytochrome P450; Data; Disease; Drug Addiction; Enzymes; Evaluation; In Vitro; Ligands; Measures; Medical; National Institute of Drug Abuse; Pharmaceutical Preparations; Ships; Site; Specific qualifier value; Structure; Testing; Therapeutic; Time; Toxic effect; Toxicology; United States; Work; addiction; biological systems; follow-up; novel; pre-clinical; programs; receptor; receptor binding; screening

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.

根据任务 1，承包商应收到最多四十五 (45) 种测试化合物，用于评估受体概况筛选。承包商应一式两份（每个目标四 (4) 个孔）以两种浓度（100 nM 和 10,000 nM）筛选这些化合物。除非项目官员另有要求，否则承包商应筛选概况中列出的生物目标的结合力。根据任务 2，承包商应对受体结合、功能活性或其他测定进行最多六十 (60) 次评估。待执行的测定的确切数量和类型通常在任务 1 工作完成后才能指定，但可能包括受体、转运蛋白和酶位点的结合和功能活性测量。每次评估应由八 (8) 个浓度的两次重复组成，每次重复使用重复的孔（每次测定总共 32 个孔），并将确定目标受体的 IC50/Ki 或功能活性。在研究之前，可以进行 100 和 10,000 nM 的筛选测定，一式两份（4 个孔）或 NIDA COR 规定的其他浓度，以帮助确定要测试的最佳浓度范围。功能测定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) 项毒性测定，包括细胞色素 P450 谱、hERG 通道测定、Ames 致突变性测定和 P-gp 底物测定。每个 Cyp450 配置文件应包括在 100 和 10,000 nM 下测试工作说明书中指定的六 (6) 个 Cyp450 酶的重复孔（总共二十四 (24) 个孔）。将在每个位点进行 Ki/IC50 评估，其中曲线显示在任一浓度下至少有百分之二十五 (25%) 的结合抑制（“命中”）。每次后续评估应由八 (8) 个浓度的两次重复组成，每次重复使用重复的孔（每次测定总共 32 个孔）。 hERG 通道测定将包含五 (5) 个浓度和一式三份的细胞（总共 15 个数据点）。根据任务 6，承包商应按照 NIDA COR 的指示购买最多五种化合物进行测试。 NIDA COR 之前将确定这些化合物无法在美国购买并在合理的时间范围内运送给承包商。