Core B Chemistry/Biochemistry/ Pharmacology Component

研究及相关-其他项目信息-项目摘要/摘要 这个核心B设施将作为一个技术和科学支助单位，为以下三个项目(1、2、3)提供支持 计划项目。它的主要目标包括：(1)化合物的重新合成和放大 量化以满足参与四个项目的研究实验室的体外和体内需求；所有 化合物将在电子计算机中进行药物性能评估(2)所有新配体的测试 对CB1和CB2大麻素受体的亲和力；(3)配体结合能力的测试 对CB1和CB2不可逆的；(4)测试一类配体作为底物或 内源性大麻失活酶抑制剂FAAH和MGL；(5)测定功能性 在cAMP实验中初步确定成功的配体的性质；(6)测定 使用肝微粒体制剂的配体；(7)在小鼠中对一组新的配体进行选择的评价 生物利用度和跨越血脑屏障的能力；以及(8)CB1拮抗剂的体内评价 (小鼠)有能力对抗激动剂的影响。在...支持下生产的化合物 核心B也将提供给该计划项目中确定的其他实验室，这些实验室的合作是 而不会对拨款产生任何影响。

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.