Core B Chemistry/Biochemistry/ Pharmacology Component

核心 B 化学/生物化学/药理学部分

• 批准号: 8742282
• 负责人: Spyros P Nikas
• 金额: $ 28.55万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8742282
• 关键词: 2-arachidonylglycerol; Active Sites; Address; Adenylate Cyclase; Affinity; Agonist; Binding; Binding Sites; Biochemical; Biochemistry; Biological Assay; Biological Availability; Blood - brain barrier anatomy; Brain; CNR1 gene; CNR2 gene; Cell Culture Techniques; Chemistry; Collaborations; Computer Simulation; Coupling; Cyclic AMP; Dose; Endocannabinoids; Enzymes; Evaluation; GTP-Binding Proteins; Goals; Grant; Human; In Vitro; Laboratories; Laboratory Research; Ligands; Liver; Measures; Membrane; Monoacylglycerol Lipases; Mus; Penetration; Pharmacology; Preparation; Program Research Project Grants; Property; Rattus; Relative (related person); Research; SR 141716A; Signal Transduction; Temperature; Testing; Time; Work; abstracting; anandamide; cost; design; fatty acid amide hydrolase; in vivo; inhibitor/antagonist; liquid chromatography mass spectrometry; natural hypothermia; novel; programs; radioligand; receptor; research study; response; scale up; therapeutic target

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. Its major goals involve: (1) the re-synthesis and scale-up of compounds in sufficient quantifies to address the in vitro and in vivo needs of the research laboratories involved in the four projects; all compounds will be evaluated in silico for their druggability properties as well (2) the testing of all new ligands for their affinities for the CB1 and CB2 cannabinoid receptors; (3) the testing of ligands for their abilities to bind irreversibly to CB1 and CB2; (4) the testing of a class of ligands for their abilities to act as substrates or inhibitors for the endocannabinoid deactivating enzymes, FAAH and MGL; (5) determining the functional properties of successful ligands initially in the cAMP assay; (6) determining the biochemical stabilities of ligands using liver microsomal preparations; (7) evaluation of a select group of novel ligands in mice for bioavailability and their ability to cross the blood brain barrier; and (8) evaluation of CB1 antagonists in vivo (mice) for their ability to antagonize the effects of an agonist. 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 设施将作为该项目三个项目（1、2、3）的技术和科学支持单位。 计划项目。其主要目标包括：（1）以足够的量重新合成和放大化合物 量化以满足四个项目所涉及的研究实验室的体外和体内需求；全部 化合物也将通过计算机评估其成药特性以及 (2) 所有新配体的测试 由于它们对 CB1 和 CB2 大麻素受体的亲和力； (3) 配体结合能力的测试 不可逆地变为 CB1 和 CB2； (4) 测试一类配体作为底物的能力或 内源性大麻素失活酶、FAAH 和 MGL 抑制剂； (5) 确定泛函 cAMP 测定中最初成功配体的特性； (6)生化稳定性测定 使用肝微粒体制剂的配体； (7) 在小鼠中评估一组选定的新型配体 生物利用度及其穿过血脑屏障的能力； (8) CB1拮抗剂的体内评价 （小鼠）因为它们具有拮抗激动剂作用的能力。在赞助下生产的化合物 核心 B 也将提供给本计划项目中确定的其他实验室，其合作是 无需支付任何费用。