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51. 发明授权

US06458926B1 Heterodimer complex of RXR and NURR1 or NGFI-B 失效
标题翻译： RXR和NURR1或NGFI-B的异二聚体复合物
公开(公告)号：US06458926B1
公开(公告)日：2002-10-01
申请号：US08877966
申请日：1997-06-18
申请人： Ronald M. Evans , Barry M. Forman , Kazuhiko Umesono
发明人： Ronald M. Evans , Barry M. Forman , Kazuhiko Umesono
IPC分类号： C07K14435
CPC分类号： C07K14/70567 , C07K2319/00 , G01N33/6875 , G01N33/74
摘要： Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T3R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T3R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurr1 heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response. These findings establish a novel 9-cis retinoic acid response pathway and resolve the paradox as to how T3R, RAR and VDR contribute to distinct physiologic pathways while sharing a common RXR subunit.
摘要翻译：异源二聚化是真核转录因子中的常见范例，尽管单个单体如何有助于复合物的整体转录活性仍不清楚。 9-顺式视黄酸受体（RXR）用作几种核受体（包括甲状腺激素（T3R），视黄酸（RAR）和维生素D受体）的常见异源二聚体配偶体。已经设计出一种策略来单独检测每个受体的转录特性，或者当连接到异二聚体配偶体时。已经发现在RXR-T3R和RXR-RAR异二聚体中RXR的固有活性被掩蔽。相比之下，本文描述的新型RXR-Nurr1异源二聚体对RXR配体具有高度响应性，表明不同的合作伙伴对RXR应答发挥独特的变构控制。这些研究结果建立了一种新的9-顺式视黄酸反应途径，并解决了T3R，RAR和VDR如何在共享一个共同的RXR亚基时对不同的生理途径有贡献的矛盾。

52. 发明授权

US06281330B1 Multimeric forms of members of the steroid/thyroid superfamily of receptors with the ultraspiracle receptor 失效
标题翻译：具有超吸收受体的受体的类固醇/甲状腺超家族成员的多聚体形式
公开(公告)号：US06281330B1
公开(公告)日：2001-08-28
申请号：US08486403
申请日：1995-06-05
申请人： Ronald M. Evans , Michael B. Mc Keown , Anthony E. Oro , William A. Segraves , Tso-Pang Yao
发明人： Ronald M. Evans , Michael B. Mc Keown , Anthony E. Oro , William A. Segraves , Tso-Pang Yao
IPC分类号： C07K500
CPC分类号： C07K14/44 , A61K38/00 , A61K48/00 , C07K14/70567 , C07K14/721 , C12N15/85 , C12N2830/00 , C12N2830/002 , C12N2830/75 , C12Q1/6897
摘要： In accordance with the present invention, it has been discovered that various members of the steroid/thyroid superfamily of receptors can interact with the insect-derived ultraspiracle receptor, to form multimeric species. Accordingly, the interaction of at least one member of the steroid/thyroid superfamily of receptors with at least the dimerization domain of the ultraspiracle receptor modulates the ability of said member of the steroid/thyroid superfamily of receptors to transactivate transcription of genes maintained under hormone expression control in the presence of the cognate ligand for said member of the superfamily.
摘要翻译：根据本发明，已经发现，受体的类固醇/甲状腺超家族的各种成员可以与昆虫来源的超吸虫受体相互作用，形成多聚体物质。因此，至少一种受体的类固醇/甲状腺超家族与至少二尖晶状体受体的二聚化结构域之间的相互作用调节所述类固醇/甲状腺超家族成员能够激活维持在激素表达下的基因转录的能力在所述超家族成员的同源配体存在下控制。

53. 发明授权

US06265173B1 Methods of modulating the expression of genes using ultraspiracle receptor 失效
标题翻译：使用超尖锐受体调节基因表达的方法
公开(公告)号：US06265173B1
公开(公告)日：2001-07-24
申请号：US08464514
申请日：1995-06-05
申请人： Ronald M. Evans , Michael B. Mc Keown , Anthony E. Oro , William A. Segraves , Tso-Pang Yao
发明人： Ronald M. Evans , Michael B. Mc Keown , Anthony E. Oro , William A. Segraves , Tso-Pang Yao
IPC分类号： C12N1585
CPC分类号： C07K14/44 , A61K38/00 , A61K48/00 , C07K14/70567 , C07K14/721 , C12N15/85 , C12N2830/00 , C12N2830/002 , C12N2830/75 , C12Q1/6897
摘要： In accordance with the present invention, it has been discovered that various members of the steroid/thyroid superfamily of receptors can interact with the insect-derived ultraspiracle receptor, to form multimeric species. Accordingly, the interaction of at least one member of the steroid/thyroid superfamily of receptors with at least the dimerization domain of the ultraspiracle receptor modulates the ability of said member of the steroid/thyroid superfamily of receptors to trans-activate transcription of genes maintained under hormone expression control in the presence of the cognate ligand for said member of the superfamily.
摘要翻译：根据本发明，已经发现，受体的类固醇/甲状腺超家族的各种成员可以与昆虫来源的超吸虫受体相互作用，形成多聚体物质。因此，至少一种受体的类固醇/甲状腺超家族与至少二尖晶状体受体的二聚化结构域之间的相互作用调节所述类固醇/甲状腺超家族受体的反式激活转录的能力，在所述超家族成员的同源配体存在下的激素表达控制。

54. 发明授权

US5939442A Modulations of peroxisome proliferator activated receptor-.gamma., and methods for the use thereof 失效
标题翻译：过氧化物酶体增殖物激活受体-γ的调节剂及其使用方法
公开(公告)号：US5939442A
公开(公告)日：1999-08-17
申请号：US477493
申请日：1995-06-07
申请人： Ronald M. Evans , Barry M. Forman
发明人： Ronald M. Evans , Barry M. Forman
IPC分类号： C07D257/04 , A61K31/395 , A61K31/41 , A61K31/425 , A61K31/44 , A61K31/4439 , A61K31/53 , A61K31/54 , A61K45/00 , A61P3/00 , A61P3/08
CPC分类号： A61K31/54 , A61K31/395 , A61K31/41 , A61K31/425 , A61K31/44 , A61K31/4439 , A61K31/53 , Y10S514/909
摘要： In accordance with the present invention, there is provided a class of compounds which are capable of modulating processes mediated by peroxisome proliferator activated receptor-gamma (PPAR-.gamma.). The identification of such compounds makes it possible to intervene in PPAR-.gamma. mediated pathways.
摘要翻译：根据本发明，提供了一类能够调节由过氧化物酶体增殖物激活受体-γ（PPAR-γ）介导的过程的化合物。这种化合物的鉴定使得可能干预PPAR-γ介导的途径。

55. 发明授权

US5906920A Methods for the detection of ligands for retinoid X receptors 失效
标题翻译：检测类视黄醇X受体配体的方法
公开(公告)号：US5906920A
公开(公告)日：1999-05-25
申请号：US520637
申请日：1995-08-29
申请人： Ronald M. Evans , Ira G. Schulman
发明人： Ronald M. Evans , Ira G. Schulman
IPC分类号： G01N33/566 , C07K14/47 , C07K14/705 , C07K19/00 , C12N15/09 , C12Q1/68 , G01N33/15 , G01N33/53
CPC分类号： C12Q1/6897 , C07K14/4702 , C07K14/70567 , C07K2319/00
摘要： The retinoid X receptor (RXR) participates in a wide array of hormonal signaling pathways either as a homodimer or as a heterodimer with other members of the steroid/thyroid hormone superfamily of receptors. In accordance with the present invention, the ligand-dependent transactivation function of RXR has been characterized and the ability of RXR to interact with components of the basal transcription machinery has been examined. In vivo and in vitro experiments indicate the RXR ligand binding domain makes a direct, specific and ligand-dependent contact with a highly conserved region of the TATA binding protein (TBP). The ability of mutations that reduce ligand-dependent transcription by RXR to disrupt the RXR-TBP interaction in vivo and in vitro suggests that RXR makes direct contact with the basal transcription machinery in order to achieve activation.
摘要翻译：类视黄醇X受体（RXR）参与各种激素信号通路，作为同二聚体或与受体的类固醇/甲状腺激素超家族的其他成员的异源二聚体。根据本发明，已经表征了RXR的配体依赖性反式激活功能，并且已经检查了RXR与基础转录机制的组分相互作用的能力。体内和体外实验表明RXR配体结合结构域与TATA结合蛋白（TBP）的高度保守区域进行直接，特异性和配体依赖性接触。通过RXR减少配体依赖性转录以破坏体内和体外RXR-TBP相互作用的突变的能力表明，RXR与基础转录机制直接接触以实现激活。

56. 发明授权

US5696233A Orphan steroid hormone receptors 失效
标题翻译：孤儿类固醇激素受体
公开(公告)号：US5696233A
公开(公告)日：1997-12-09
申请号：US463694
申请日：1995-06-05
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 , C07K14/72
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。

57. 发明授权

US5641652A Insect retinoid-like receptor compositions and methods 失效
标题翻译：类视黄醇样受体组成和方法
公开(公告)号：US5641652A
公开(公告)日：1997-06-24
申请号：US464266
申请日：1995-06-05
申请人： Anthony E. Oro , Ronald M. Evans
发明人： Anthony E. Oro , Ronald M. Evans
IPC分类号： C07K14/705 , C12P21/06 , C07K1/00 , C12N5/00
CPC分类号： C07K14/70567
摘要： The present invention relates to the discovery of novel insect receptor polypeptides, which, when complexed with certain ligands, or otherwise activated by certain compounds, modulate transcription of certain genes by binding to cognate response elements associated with the promoters of the genes. The novel receptors of the invention are substantially similar to previously discovered mammalian receptors which are activated to modulate transcription of certain genes in cells, when the cells are exposed to retinoic acid. The invention provides DNAs encoding the novel receptors, including expression vectors for expression of the receptors in cells; cells transformed with such expression vectors; cells co-transformed with such expression vectors and with reporter vectors to monitor activation of the receptors to modulate transcription, when the cells are exposed to ligand for the invention receptor; and methods of using such co-transformed cells in screening for compounds which are capable of leading to activation of the receptors and for compounds which are capable of interfering with such activation and, as such, are potentially potent insecticides. The invention also provides DNA and RNA probes for identifying DNA's encoding related receptors, of insects and other animals, of the class, to which the novel receptors of the invention belong.
摘要翻译：本发明涉及新型昆虫受体多肽的发现，当与某些配体复合或被某些化合物激活时，可通过结合与基因启动子相关的同源反应元件调节某些基因的转录。本发明的新型受体基本上类似于先前发现的哺乳动物受体，其在细胞暴露于视黄酸时被活化以调节细胞中某些基因的转录。本发明提供编码新受体的DNA，包括用于在细胞中表达受体的表达载体; 用这种表达载体转化的细胞; 当细胞暴露于本发明受体的配体时，与这些表达载体共同转化的细胞和报告载体以监测受体的活化以调节转录; 以及使用这种共转化细胞筛选能够导致受体活化的化合物和能够干扰这种活化并且因此是潜在有效的杀虫剂的化合物的方法。本发明还提供用于鉴定本发明的新受体所属的类别的昆虫和其他动物的DNA编码相关受体的DNA和RNA探针。

58. 发明授权

US5578483A Receptor transcription-repression activity compositions and methods 失效
标题翻译：受体转录抑制活性组合物和方法
公开(公告)号：US5578483A
公开(公告)日：1996-11-26
申请号：US691043
申请日：1991-06-21
申请人： Ronald M. Evans , Stanley M. Hollenberg , Anthony E. Oro
发明人： Ronald M. Evans , Stanley M. Hollenberg , Anthony E. Oro
IPC分类号： A01K67/027 , A61K38/00 , A61K48/00 , C07K14/435 , C07K14/705 , C07K14/72 , C07K19/00 , C12N5/10 , C12N15/09 , C12P21/02 , C12N5/16 , C12N15/85
CPC分类号： C07K14/721 , C07K19/00 , C07K2319/00 , C07K2319/61 , C07K2319/715 , C07K2319/81
摘要： Disclosed is an analysis of domains of receptors of the steroid/thyroid hormone superfamily, and particularly of the glucocorticoid receptor, to identify requirements for the trans-acting transcriptional repression activities of the receptors. Based on the analysis, certain novel receptor analogs are provided, as are various novel DNAs, expression vectors, cells and transgenic animals as well as novel methods of using trans-acting transcription-repressing analogs of the receptors in various applications. These applications include gene therapy, screening of cells in culture or transgenic animals for compositions effective to treat various diseases due to inability to properly respond to hormones of the steroid or thyroid hormone group, and screening of cells in culture for ligands that are capable, upon binding to one of the receptors, to activate its trans-acting transcription activating and trans-acting transcription-repressing activities.
摘要翻译：公开了对类固醇/甲状腺激素超家族，特别是糖皮质激素受体的受体结构域的分析，以鉴定受体的反式作用转录抑制活性的要求。基于分析，提供某些新的受体类似物，以及各种新型DNA，表达载体，细胞和转基因动物以及在各种应用中使用受体的反式作用转录抑制类似物的新方法。这些应用包括基因治疗，筛选培养物中的细胞或转基因动物，用于由于不能适当地对类固醇或甲状腺激素基团的激素进行适当反应而有效治疗各种疾病的组合物，以及筛选培养中的细胞，与其中一种受体结合，激活其反式作用转录激活和反式作用转录抑制活性。

59. 发明授权

US5530094A Gamma retinoic acid receptor 失效
标题翻译： γ视黄酸受体
公开(公告)号：US5530094A
公开(公告)日：1996-06-25
申请号：US100039
申请日：1993-07-30
申请人： Fumimaro Takaku , Takashi Ishikawa , Michio Imawari , Ronald M. Evans , Kazuhiko Umesono
发明人： Fumimaro Takaku , Takashi Ishikawa , Michio Imawari , Ronald M. Evans , Kazuhiko Umesono
IPC分类号： A61K38/00 , C07K14/00 , C07K14/705 , C07K14/72 , C07K19/00 , C12N5/10 , C12N15/09 , C12P21/02 , C12R1/91 , C07G1/00 , C12N15/00 , C12P21/06
CPC分类号： C07K14/72 , C07K14/70567 , C07K14/721 , A61K38/00 , C07K2319/00 , C07K2319/715 , C07K2319/80 , Y10S530/826 , Y10S530/846
摘要： A novel gamma retinoic acid receptor is disclosed. The novel receptor is encoded for by cDNA carried on plasmid pGEM-hRAR.gamma., which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera contain at least one functional domain from the new gamma retinoic acid receptor.
摘要翻译：公开了一种新型的视黄酸受体。新型受体由携带在质粒pGEM-hRARγ上的cDNA编码，其已经保藏在美国典型培养物保藏中心用于专利。还公开了嵌合受体蛋白。嵌合体含有来自新的视黄酸受体的至少一个功能结构域。

60. 发明授权

US4737578A Human inhibin 失效
标题翻译：人抑制素
公开(公告)号：US4737578A
公开(公告)日：1988-04-12
申请号：US848924
申请日：1986-04-07
申请人： Ronald M. Evans , Michael G. Rosenfeld , Gail Cerelli , Kelly E. Mayo , Joachim Spiess , Jean E. F. Rivier , Wylie W. Vale, Jr.
发明人： Ronald M. Evans , Michael G. Rosenfeld , Gail Cerelli , Kelly E. Mayo , Joachim Spiess , Jean E. F. Rivier , Wylie W. Vale, Jr.
IPC分类号： A61K38/00 , C07K14/575 , C07K7/10 , C07K13/00
CPC分类号： C07K14/575 , A61K38/00 , Y10S930/26
摘要： Proteins with inhibin activity having a weight of about 32,000 daltons. The molecule is composed of two chains having molecular weights of about 18,000 and about 14,000 daltons, respectively, which are bound together by disulfide bonding. The 18K chain is obtained from the human inhibin gene and has the formula: H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu-Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Leu-Asn-Ile-Ser-Phe-Gln-Glu-Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R.sub.65 -Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His-Ile-Pro-Pro-Asn-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly-Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pro-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly-Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH, wherein R.sub.65 is Ile or Arg. The 18K chain is connected by disulfide bonding to the 14K chain.
摘要翻译：具有约32,000道尔顿重量的具有抑制素活性的蛋白质。该分子由分子量分别为约18,000和约14,000道尔顿的两条链组成，它们通过二硫键结合在一起。 18K链由人抑制素基因得到，具有下式：H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Le-Asn-Ile-Ser-Phe-Gln-Glu- Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R65-Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His- Ile-Pro-Pro-As n-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly -Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pr-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly- Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH，其中R65是Ile或Arg。 18K链通过二硫键与14K链连接。

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