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公开(公告)号:US07256007B2
公开(公告)日:2007-08-14
申请号:US10221125
申请日:2001-03-09
申请人: Sandra Elaine Nicholson , Manuel Baca , Nicos A. Nicola , Douglas Hilton , Jian Guo Zhang , Louis Fabri , Andrew Nash
发明人: Sandra Elaine Nicholson , Manuel Baca , Nicos A. Nicola , Douglas Hilton , Jian Guo Zhang , Louis Fabri , Andrew Nash
CPC分类号: G01N33/6863
摘要: The present invention relates generally to a method for regulating cytokine signaling and agents useful for same. The method of the present invention is predicated in part on the identification of the molecular target of suppressor of cytokine signaling (SOCS) interaction in controlling cytokine signaling. The identification of the molecular target permits the development of assays to screen for a range of agonists and antagonists useful in modulating cytokine function. The present invention further provides, therefore, screening assays and more particularly high through-put screening assays for agonists and antagonists of SOCS-receptor interaction. Such agonists and antagonists are useful in the manufacture of medicaments for controlling cytokine signaling. Control of cytokine signaling is important for the treatment of a range of conditions including cancer, inflammatory conditions, immunological disorders and any other conditions involving aberrations of signal transduction.
摘要翻译: 本发明一般涉及用于调节细胞因子信号传导的方法和可用于其的试剂。 本发明的方法部分地基于在控制细胞因子信号传导中识别细胞因子信号传导抑制剂(SOCS)相互作用的分子靶标。 分子靶标的鉴定允许开发测定以筛选可用于调节细胞因子功能的一系列激动剂和拮抗剂。 因此,本发明进一步提供用于SOCS-受体相互作用的激动剂和拮抗剂的筛选测定和更特别的高通量筛选测定。 这样的激动剂和拮抗剂可用于制备用于控制细胞因子信号传导的药物。 细胞因子信号传导的控制对于治疗一系列病症(包括癌症,炎性病症,免疫学障碍和涉及信号转导异常的任何其他病症)是重要的。
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公开(公告)号:US07078174B1
公开(公告)日:2006-07-18
申请号:US09868813
申请日:1999-12-21
申请人: Tracy Ann Willson , Richard John Simpson , Alison Mary Farley , Sandra Elaine Nicholson , Jian-Guo Zhang , Manuel Baca , Nicos A. Nicola , Douglas J. Hilton , Warren Scott Alexander , Donald Metcalf
发明人: Tracy Ann Willson , Richard John Simpson , Alison Mary Farley , Sandra Elaine Nicholson , Jian-Guo Zhang , Manuel Baca , Nicos A. Nicola , Douglas J. Hilton , Warren Scott Alexander , Donald Metcalf
IPC分类号: G01N33/53 , G01N33/567
CPC分类号: C07K14/4703 , A01K2217/05 , A61K38/00
摘要: The present invention relates generally to amino acid sequences obtainable from SOCS proteins and which are capable of interacting with intracellular molecules. The present invention further relates to nucleic acid molecules encoding said amino acid sequences. The amino acid sequences and the nucleic acid molecules encoding same of the present invention are useful in modulating degradation of proteinaceous molecules such as but not limited to SOCS proteins and proteinaceous molecules associated therewith. The present invention provides a mechanism for modulating cytokine or cytokine-like molecule signalling by modulating the degradation of activated signal transduction molecules or their negative regulators, i.e. the SOCS proteins.
摘要翻译: 本发明一般涉及可从SOCS蛋白获得并且能够与细胞内分子相互作用的氨基酸序列。 本发明还涉及编码所述氨基酸序列的核酸分子。 编码本发明的氨基酸序列和核酸分子可用于调节蛋白质分子的降解,例如但不限于与其相关的SOCS蛋白和蛋白质分子。 本发明提供了通过调节活化的信号转导分子或其负调节物(即SOCS蛋白)的降解来调节细胞因子或细胞因子样分子信号传导的机制。
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公开(公告)号:US07517959B2
公开(公告)日:2009-04-14
申请号:US11598212
申请日:2006-11-09
申请人: Raymond Stanley Norton , Jeffrey James Babon , Sandra Elaine Nicholson , Nicos Anthony Nicola , Edward James McManus , Manuel Baca , Shenggen Yao
发明人: Raymond Stanley Norton , Jeffrey James Babon , Sandra Elaine Nicholson , Nicos Anthony Nicola , Edward James McManus , Manuel Baca , Shenggen Yao
CPC分类号: C07K14/4703 , A61K38/17
摘要: The present invention relates to the identification of a PEST motif in Suppressor of Cytokine Signalling (SOCS) proteins, the deletion/inactivation of which has been found to increase the stability of the protein whilst maintaining at least one biological activity of the protein. Such SOCS proteins with deleted/inactivated PEST motifs can be used in gene and protein therapy procedures to provide a more stable SOCS protein when compared to the native protein. The present invention also relates to the characterization of the structure of SOCS proteins, and methods of using this structural information to identify compounds which modulate the activity of SOCS.
摘要翻译: 本发明涉及鉴定细胞因子信号传导抑制因子(SOCS)蛋白质的抑制因子的PEST基序,已经发现其缺失/失活增加了蛋白质的稳定性,同时保持蛋白质的至少一种生物学活性。 具有缺失/失活的PEST基序的这种SOCS蛋白质可用于基因和蛋白质治疗程序,以便与天然蛋白质相比提供更稳定的SOCS蛋白质。 本发明还涉及SOCS蛋白质结构的表征,以及使用该结构信息鉴定调节SOCS活性的化合物的方法。
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公开(公告)号:US20120308570A1
公开(公告)日:2012-12-06
申请号:US13319090
申请日:2010-05-06
IPC分类号: A61K38/17 , C07K7/08 , C07K16/18 , A61K39/395 , A61K38/08 , G01N24/08 , A61P11/00 , A61P29/00 , C12N5/071 , G01N33/566 , G01N33/573 , G01N21/55 , C07K14/435 , A61P11/06
CPC分类号: C07K16/40 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0337 , A61K38/00 , C07K14/47 , C12N9/0075 , C12N15/113 , C12N2310/14 , C12N2310/531 , C12Y114/13039 , G01N2500/02
摘要: The present invention relates to methods of modulating the level of inducible nitric oxide synthase (iNOS) in a cell which comprises administering to the cell a compound which modulates binding of SPRY domain-containing SOCS box protein (SSB) to iNOS, and/or a compound which modulates SSB activity in the cell. Further provided are methods of treating or preventing disease in a subject by modulating the level of iNOS in a cell, as well as compounds which modulate binding of SSB to iNOS and compounds which modulate SSB activity.
摘要翻译: 本发明涉及调节细胞中诱导型一氧化氮合酶(iNOS)水平的方法,其包括向细胞施用调节含有SPRY结构域的SOCS盒蛋白(SSB)与iNOS的结合的化合物和/或 调节细胞中SSB活性的化合物。 还提供了通过调节细胞中iNOS的水平以及调节SSB与iNOS的结合的化合物和调节SSB活性的化合物来治疗或预防受试者的疾病的方法。
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