Chemistry/Biochemistry/Pharmacology Core

化学/生物化学/药理学核心

• 批准号: 10680369
• 负责人: Spyros P Nikas
• 金额: $ 36.55万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680369
• 关键词: 2-arachidonylglycerol; ABHD6 gene; Acceleration; Active Sites; Address; Adenylate Cyclase; Affinity; Agonist; Animals; Binding; Biochemistry; Biological Assay; Biological Availability; Brain; CNR1 gene; CNR2 gene; Carrier Proteins; Cells; Characteristics; Chemistry; Classification; Collaborations; Cyclic AMP; Doctor of Philosophy; Drug Kinetics; Endocannabinoids; Ensure; Enzymes; Evaluation; G-Protein-Coupled Receptors; Glycerol; Goals; Grant; Human; Hydrolase; In Vitro; Individual; Ion Channel; Laboratories; Laboratory Research; Letters; Ligands; Lipase; Liver Microsomes; Measures; Membrane; Metabolic; Modeling; Mus; Pharmacodynamics; Pharmacology; Plasma; Positioning Attribute; Preparation; Program Research Project Grants; Property; Rattus; Research; Secure; Signal Transduction; Testing; Transfection; Work; analog; anandamide; antagonist; cost; endocannabinoid deactivating enzyme; fatty acid amide hydrolase; in vivo; novel; pharmacologic; positive allosteric modulator; programs; receptor; receptor binding; scale up; screening; therapeutic target; tool

RESEARCH & RELATED - OTHER PROJECT INFORMATION - PROJECT SUMMARY/ABSTRACT This Core B facility will serve as a technical and scientific support unit for the three Projects (1, 2, 3) of this Program Project Grant. Its major goals involve: (1) the re-synthesis and scale-up of compounds in sufficient quantities to address the in vitro and in vivo needs of the research laboratories involved in the projects; (2) the testing of all new orthosteric ligands for their affinities for the CB1 and CB2 cannabinoid receptors; (3) the testing of orthosteric ligands for their abilities to bind irreversibly/tightly to CB1 and CB2; (4) determining the functional properties of ligands initially in the cAMP assay (both orthosteric and allosteric); (5) the testing of anandamide analogs for their abilities to act as substrates of the endocannabinoid deactivating enzyme, FAAH; (6) determining the metabolic and plasma stabilities of ligands using liver microsomal and plasma preparations, respectively; (7) screening for off-target interactions against a broad panel of G protein-coupled receptors, ion channels, transport proteins as well as endocannabinoid metabolizing enzymes; and (8) evaluation of a select group of novel ligands in mice for their bioavailability in CNS and plasma; the top candidates of each class in an extensive pharmacokinetic profiling. Compounds produced under the auspices of Core B will also be made available to other laboratories identified in this Program Project whose collaboration is at no cost to the grant.

研究与相关 - 其​​他项目信息 - 项目摘要/摘要 该核心 B 设施将作为本项目三个项目（1、2、3）的技术和科学支持单位。 计划项目补助金。其主要目标包括：（1）以足够的量重新合成和放大化合物 满足参与项目的研究实验室的体外和体内需求的数量； （2） 测试所有新的正构配体对 CB1 和 CB2 大麻素受体的亲和力； (3) 测试 正位配体具有不可逆/紧密结合 CB1 和 CB2 的能力； (4) 确定泛函 cAMP 测定中最初配体的特性（正构和变构）； (5)花生四烯酸乙醇胺的检测 类似物能够作为内源性大麻素失活酶 FAAH 的底物； (6) 使用肝微粒体和血浆制剂测定配体的代谢和血浆稳定性， 分别; (7) 筛选针对广泛的 G 蛋白偶联受体、离子的脱靶相互作用 通道、转运蛋白以及内源性大麻素代谢酶； (8) 选定的评估 一组新型配体在小鼠中的中枢神经系统和血浆中的生物利用度；每个班级的顶尖候选人 广泛的药代动力学分析。在 Core B 的支持下生产的化合物也将被制造 可供本计划项目中确定的其他实验室使用，其合作不需支付任何费用。