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1. 发明申请

US20050193433A1 Compositions and methods of modulating cholesterol metabolism 有权
标题翻译：调节胆固醇代谢的组成和方法
公开(公告)号：US20050193433A1
公开(公告)日：2005-09-01
申请号：US11021728
申请日：2004-12-22
申请人： David Mangelsdorf , Joyce Repa , Stephen Turley , John Dietschy
发明人： David Mangelsdorf , Joyce Repa , Stephen Turley , John Dietschy
IPC分类号： C07K14/705 , C12N15/85 , C12Q1/68 , A01K67/027
CPC分类号： C07K14/70567 , A01K67/0276 , A01K2217/05 , A01K2217/075 , A01K2227/10 , A01K2227/105 , A01K2267/0306 , A01K2267/0362 , C12N15/8509 , C12N2830/008 , C12N2830/48
摘要： The present invention relates to compositions and methods for reducing cholesterolemia and its effects. More specifically, the invention is directed, in one embodiment, to methods for screening for compounds that affect cholesterol levels generally, and in particular, that affect the absorption of cholesterol. The invention also is directed to methods of screening for compounds that increase bile acid synthesis. In so doing, the inventors describe useful transgenic cells and animals which lack one or both alleles of the LXRα gene. Also provided are therapeutic methods designed to reduce cholesterol levels in suitable subjects. The reduction may be effected by decreasing cholesterol absorption, increasing bile acid synthesis, or combinations thereof. Particularly useful in decreasing cholesterol absorption are RXR agonists, for example, rexinoid compounds. Therapeutic intervention in cholesterol biosynthesis and diet are additional adjunct therapies. In addition, the present invention relates to candidate compounds that modulate the expression of ABC-1 in a cell that expresses RXR. Methods of identifying and making a modulator of ABC-1 are disclosed.
摘要翻译：本发明涉及降低胆固醇血症及其作用的组合物和方法。更具体地，在一个实施方案中，本发明涉及用于筛选通常影响胆固醇水平的化合物的方法，特别是影响胆固醇吸收的化合物的方法。本发明还涉及筛选增加胆汁酸合成的化合物的方法。这样做时，本发明人描述了缺乏LXRα基因的一个或两个等位基因的有用的转基因细胞和动物。还提供了旨在降低合适受试者的胆固醇水平的治疗方法。还原可通过降低胆固醇吸收，增加胆汁酸合成或其组合来实现。特别可用于降低胆固醇吸收的是RXR激动剂，例如类毒素化合物。胆固醇生物合成和饮食的治疗干预是额外的辅助疗法。此外，本发明涉及调节表达RXR的细胞中ABC-1表达的候选化合物。公开了鉴定和制备ABC-1调节剂的方法。

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