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1. 发明申请

WO1997007212A1 OPIOID ANTAGONISTS AND METHODS OF THEIR USE 审中-公开
标题翻译： OPIOI ANTAGONISTS及其使用方法
公开(公告)号：WO1997007212A1
公开(公告)日：1997-02-27
申请号：PCT/US1996013305
申请日：1996-08-12
申请人： OREGON HEALTH SCIENCES UNIVERSITY
发明人： OREGON HEALTH SCIENCES UNIVERSITY , GRISEL, Judith, E. , MOGIL, Jeffrey, S. , GRANDY, David, K. , BUNZOW, James, R. , CIVELLI, Olivier , REINSCHEID, Rainer, Klaus , NOTHACKER, Hans-Peter , MONSMA, Frederick, James
IPC分类号： C12N15/12
CPC分类号： C07K14/665 , A61K38/00
摘要： The present invention relates to a novel mammalian anti-opioid receptor protein (OFQR), peptide ligands (such as OFQ) that bind to OFQR, and methods of using the OFQ peptide and analogues to reverse the physiologic effects of opiates such as morphine. The isolation, characterization and pharmacological use of the endogenous peptide ligand is described. A particular embodiment of the OFQ peptide is a heptadecapeptide having an FGGF aminoterminal motif. The peptide specifically binds to an OFQ receptor protein heterologously expressed in mammalian cells. The peptide does not bind with high affinity to mu , delta or kappa receptors, but it antagonizes opioid mediated effects (such as analgesia and hypothermia) without increasing nociceptive sensitivity. Tyrosine substitution variants of the peptide ligand specifically bind to the opioid receptor and can be radioiodinated. Also provided are methods of making such peptide ligands and OFQR antagonists, and methods of using the ligands for diagnostic and therapeutic uses and for the identification of other naturally-occurring or synthetic opioid receptor ligands.
摘要翻译：本发明涉及新型哺乳动物抗阿片类受体蛋白（OFQR），与OFQR结合的肽配体（如OFQ），以及使用OFQ肽和类似物逆转阿片剂如吗啡的生理作用的方法。描述了内源肽配体的分离，表征和药理学应用。 OFQ肽的具体实施方案是具有FGGF氨基末端基序的十七肽。该肽特异性结合在哺乳动物细胞中异源表达的OFQ受体蛋白。肽不能以高亲和力结合mu，δ或κ受体，但是它不会增加伤害敏感性，而是拮抗阿片样物质介导的作用（如镇痛和低体温）。肽配体的酪氨酸取代变体与阿片受体特异性结合，可以放射性碘化。还提供了制备这种肽配体和OFQR拮抗剂的方法，以及使用该配体进行诊断和治疗用途以及鉴定其它天然存在或合成的阿片受体配体的方法。

2. 发明授权

EP0843726B1 OPIOID ANTAGONISTS AND METHODS OF THEIR USE 失效
标题翻译：阿片受体拮抗剂和申请流程。
公开(公告)号：EP0843726B1
公开(公告)日：2006-04-12
申请号：EP96928209.4
申请日：1996-08-12
申请人： OREGON HEALTH SCIENCES UNIVERSITY
发明人： GRISEL, Judith, E. , MOGIL, Jeffrey, S. , GRANDY, David, K. , BUNZOW, James, R. , CIVELLI, Olivier , REINSCHEID, Rainer, Klaus , NOTHACKER, Hans-Peter , MONSMA, Frederick, James
IPC分类号： C12N15/12 , C07K14/665 , A61K38/17 , G01N33/50
CPC分类号： C07K14/665 , A61K38/00
摘要： The present invention relates to a novel mammalian anti-opioid receptor protein (OFQR), peptide ligands (such as OFQ) that bind to OFQR, and methods of using the OFQ peptide and analogues to reverse the physiologic effects of opiates such as morphine. The isolation, characterization and pharmacological use of the endogenous peptide ligand is described. A particular embodiment of the OFQ peptide is a heptadecapeptide having an FGGF aminoterminal motif. The peptide specifically binds to an OFQ receptor protein heterologously expressed in mammalian cells. The peptide does not bind with high affinity to mu , delta or kappa receptors, but it antagonizes opioid mediated effects (such as analgesia and hypothermia) without increasing nociceptive sensitivity. Tyrosine substitution variants of the peptide ligand specifically bind to the opioid receptor and can be radioiodinated. Also provided are methods of making such peptide ligands and OFQR antagonists, and methods of using the ligands for diagnostic and therapeutic uses and for the identification of other naturally-occurring or synthetic opioid receptor ligands.

3. 发明公开

EP0843726A1 OPIOID ANTAGONISTS AND METHODS OF THEIR USE 失效
标题翻译：安东尼·安德烈·安德鲁
公开(公告)号：EP0843726A1
公开(公告)日：1998-05-27
申请号：EP96928209.0
申请日：1996-08-12
申请人： OREGON HEALTH SCIENCES UNIVERSITY
发明人： GRISEL, Judith, E. , MOGIL, Jeffrey, S. , GRANDY, David, K. , BUNZOW, James, R. , CIVELLI, Olivier , REINSCHEID, Rainer, Klaus , NOTHACKER, Hans-Peter , MONSMA, Frederick, James
IPC分类号： C12N15 , A61K38 , A61K51 , A61P25 , A61P39 , C07K14 , C12N5
CPC分类号： C07K14/665 , A61K38/00
摘要： The present invention relates to a novel mammalian anti-opioid receptor protein (OFQR), peptide ligands (such as OFQ) that bind to OFQR, and methods of using the OFQ peptide and analogues to reverse the physiologic effects of opiates such as morphine. The isolation, characterization and pharmacological use of the endogenous peptide ligand is described. A particular embodiment of the OFQ peptide is a heptadecapeptide having an FGGF aminoterminal motif. The peptide specifically binds to an OFQ receptor protein heterologously expressed in mammalian cells. The peptide does not bind with high affinity to ν, δ or λ receptors, but it antagonizes opioid mediated effects (such as analgesia and hypothermia) without increasing nociceptive sensitivity. Tyrosine substitution variants of the peptide ligand specifically bind to the opioid receptor and can be radioiodinated. Also provided are methods of making such peptide ligands and OFQR antagonists, and methods of using the ligands for diagnostic and therapeutic uses and for the identification of other naturally-occurring or synthetic opioid receptor ligands.
摘要翻译：本发明涉及一种新型哺乳动物抗阿片类受体蛋白（OFQR），与OFQR结合的肽配体（如OFQ），以及使用OFQ肽和类似物逆转阿片剂如吗啡的生理作用的方法。描述了内源肽配体的分离，表征和药理学应用。 OFQ肽的具体实施方案是具有FGGF氨基末端基序的十七肽。该肽特异性结合在哺乳动物细胞中异源表达的OFQ受体蛋白。肽不能以高亲和力结合到mu，δ或κ受体，但它拮抗阿片样物质介导的作用（如镇痛和低体温），而不增加伤害敏感性。肽配体的酪氨酸取代变体特异性结合阿片受体并可以放射性碘化。还提供了制备这种肽配体和OFQR拮抗剂的方法，以及使用该配体进行诊断和治疗用途以及鉴定其它天然存在或合成的阿片受体配体的方法。

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