Chemistry/Biochemistry/Pharmacology Core

研究及相关-其他项目信息-项目概要/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）在足够的条件下重新合成和放大化合物 （2）满足参与项目的研究实验室的体外和体内需求; 测试所有新的正构配体对CB 1和CB 2大麻素受体的亲和力;（3）测试 正构配体与CB 1和CB 2不可逆/紧密结合的能力;（4）确定正构配体的功能性， cAMP测定中最初配体的性质（正构和变构）;（5）大麻素的测试 类似物作为内源性大麻素失活酶FAAH底物的能力;（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， （7）筛选针对一组广泛的G蛋白偶联受体、离子受体和受体的脱靶相互作用。 通道、转运蛋白以及内源性大麻素代谢酶;和（8）评价选择的 一组新的配体在小鼠中的CNS和血浆中的生物利用度; 广泛的药代动力学分析。还将制造在核心B的赞助下生产的化合物 提供给本计划项目中确定的其他实验室，其合作不需要赠款。

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.