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11. 发明授权

US5747661A Retinoid-inducible response elements 失效
标题翻译：类视黄醇诱导型应答元件
公开(公告)号：US5747661A
公开(公告)日：1998-05-05
申请号：US373935
申请日：1995-01-13
申请人： Ronald M. Evans , David J. Mangelsdorf , Patricia J. Willy
发明人： Ronald M. Evans , David J. Mangelsdorf , Patricia J. Willy
IPC分类号： A61K38/00 , C07K14/705 , C12N15/85
CPC分类号： C07K14/70567 , A61K38/00
摘要： The characterization of LXR.alpha., an orphan member of the nuclear hormone receptor superfamily that can function as a tissue-specific mediator of 9-cis retinoic acid (9cRA) is described herein. When expressed in cells, LXR.alpha. activates transcription in response to 9cRA on a distinct response element, termed an LXRE. Significantly, neither RXR homodimers nor RXR/RAR heterodimers are able to substitute for LXR.alpha. in mediating this retinoid response. The LXR.alpha. response to retinoids is due to its unique interaction with endogenous RXR. This interaction shifts RXR from its previously described role as a silent, heterodimer partner to an active ligand binding partner, thus defining a novel retinoid response pathway.
摘要翻译：本文描述了可用作9-顺式视黄酸（9cRA）的组织特异性介质的核激素受体超家族的孤儿成员的LXRα的表征。当在细胞中表达时，LXRα响应于9cRA在不同的响应元件（称为LXRE）上激活转录。值得注意的是，RXR同源二聚体和RXR / RAR异源二聚体都不能在介导这种类视黄醇反应中替代LXRα。对类维生素A的LXRα反应是由于其与内源性RXR的独特相互作用。这种相互作用将RXR从其先前描述的作为静默的异二聚体配偶体的作用转移到活性配体结合配偶体，从而定义了新的维甲酸反应途径。

12. 发明授权

US5571696A Receptors 失效
标题翻译：受体
公开(公告)号：US5571696A
公开(公告)日：1996-11-05
申请号：US333358
申请日：1994-11-02
申请人： Ronald M. Evans , David J. Mangelsdorf , Estelita S. Ong , Anthony E. Oro , Uwe K. Borgmeyer , Vincent Giguere , Tso-Pang Yao
发明人： Ronald M. Evans , David J. Mangelsdorf , Estelita S. Ong , Anthony E. Oro , Uwe K. Borgmeyer , Vincent Giguere , Tso-Pang Yao
IPC分类号： C07K14/705 , C12N15/12 , C12Q1/68 , C12P21/06 , C07H17/00 , C12N5/00 , C12N15/00
CPC分类号： C07K14/70567 , C12Q1/6897 , C07K2319/00
摘要： Novel members of the steroid/thyroid superfamily of receptors are described. DNA sequences encoding same, expression vectors containing such DNA and host cells transformed with such expression vectors are also disclosed, as are methods for the expression of the novel receptors of the invention, and various uses thereof.
摘要翻译：描述了类固醇/甲状腺超家族的新成员。还公开了编码该DNA的DNA序列，含有这种DNA的表达载体和用这些表达载体转化的宿主细胞，以及本发明的新型受体的表达方法及其各种用途。

13. 发明授权

US5723329A DNA encoding retinoid receptor X (RXR) alpha and gamma; corresponding vectors and host cells 失效
标题翻译：编码类视黄醇受体X（RXR）α和γ的DNA; 相应的载体和宿主细胞
公开(公告)号：US5723329A
公开(公告)日：1998-03-03
申请号：US336408
申请日：1994-11-08
申请人： David J. Mangelsdorf , Ronald M. Evans
发明人： David J. Mangelsdorf , Ronald M. Evans
IPC分类号： C07H21/04 , C07K14/00 , C07K14/705 , C12N5/10 , C12N15/09 , C12N15/12 , C12N15/64 , C12N15/67 , C12N15/85 , C12P21/02 , C12Q1/68 , C12R1/91
CPC分类号： C07K14/70567 , C12N15/64 , C12N15/67 , C12N15/85 , C12N2830/00 , C12N2830/002 , C12N2830/75
摘要： The present invention relates to novel receptor polypeptides, which, upon interaction with certain ligands, or activation by certain compounds, modulate transcription of certain genes by binding to cognate response elements associated with promoters of such genes. The novel receptors of the invention modulate transcription in the presence of retinoid compounds. The receptors of the present invention differ significantly from known retinoic acid receptors, in protein primary sequence and in responsiveness to exposure to various retinoids. The invention provides DNAs encoding the novel receptors, expression vectors for expression of the receptors, cells transformed with such expression vectors, cells co-transformed with such expression vectors and with reporter vectors to monitor modulation of transcription by the receptors, and methods of using such co-transformed cells in screening for compounds which are capable, directly or indirectly, of activating the receptors. The invention also provides nucleic acid probes for identifying DNAs which encode additional retinoid receptors of the same class as the novel receptors disclosed herein.
摘要翻译：本发明涉及新的受体多肽，其在与某些配体相互作用或某些化合物的活化时，通过结合与这些基因的启动子相关的同源反应元件来调节某些基因的转录。本发明的新受体在类视色素化合物存在下调节转录。本发明的受体与已知的视黄酸受体显着不同，蛋白质一级序列和对各种类视黄醇的暴露反应。本发明提供了编码新受体的DNA，用于表达受体的表达载体，用这种表达载体转化的细胞，用这些表达载体共转化的细胞和用报道载体监测受体转录的调节的方法共转化细胞筛选能够直接或间接激活受体的化合物。本发明还提供用于鉴定编码与本文公开的新型受体相同类别的另外的类视黄醇受体的DNA的核酸探针。

14. 发明授权

US08007994B2 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：US08007994B2
公开(公告)日：2011-08-30
申请号：US11021728
申请日：2004-12-22
申请人： David J. Mangelsdorf , Joyce J. Repa , Stephen D. Turley , John M. Dietschy
发明人： David J. Mangelsdorf , Joyce J. Repa , Stephen D. Turley , John M. Dietschy
IPC分类号： C12N5/00 , C12N15/00 , G01N33/53 , C12Q1/00
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。

15. 发明授权

US07825269B2 Ligands for nematode nuclear receptors and uses thereof 有权
标题翻译：用于线虫核受体的配体及其用途
公开(公告)号：US07825269B2
公开(公告)日：2010-11-02
申请号：US11683742
申请日：2007-03-08
申请人： David J. Mangelsdorf , Richard J. Auchus , Daniel L. Motola , Carolyn L. Cummins , Kamalesh K. Sharma
发明人： David J. Mangelsdorf , Richard J. Auchus , Daniel L. Motola , Carolyn L. Cummins , Kamalesh K. Sharma
IPC分类号： C07J9/00
CPC分类号： A61K31/575 , C07J9/00 , C07J9/005 , Y02P20/582
摘要： Anti-nematode compounds, compositions, and methods for identifying such compounds are disclosed, where the compounds have the formula I: where Q, Q′, R1, R2, and n are defined herein.
摘要翻译：公开了用于鉴定此类化合物的抗线虫化合物，组合物和方法，其中化合物具有式I：其中Q，Q'，R 1，R 2和n如本文所定义。

16. 发明授权

US06835866B1 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：US06835866B1
公开(公告)日：2004-12-28
申请号：US09460292
申请日：1999-12-10
申请人： David J. Mangelsdorf , Joyce J. Repa , Stephen D. Turley , John M. Dietschy
发明人： David J. Mangelsdorf , Joyce J. Repa , Stephen D. Turley , John M. Dietschy
IPC分类号： C12P2100
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 LXR&agr; 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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