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公开(公告)号：US20140248268A1
公开(公告)日：2014-09-04
申请号：US14278468
申请日：2014-05-15
申请人： Angela Wandinger-Ness , Larry Sklar , Jacob Agola , Zurab Surviladze , Jeffrey Aube , Jennifer Golden , Chad E. Schroeder , Denise S. Simpson
发明人： Angela Wandinger-Ness , Larry Sklar , Jacob Agola , Zurab Surviladze , Jeffrey Aube , Jennifer Golden , Chad E. Schroeder , Denise S. Simpson
IPC分类号： C07D495/04 , A61K45/06 , A61K31/381
CPC分类号： C07D495/04 , A61K31/381 , A61K45/06
摘要： This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.
摘要翻译： 本发明涉及化合物及其作为Rab7 GTPase的抑制剂或活化剂的用途，用于治疗或预防Rab 7 GTP酶相关疾病如神经病变，癌症，骨骼和脂质储存代谢疾病的发生。 本发明也适用于Rab7灭活或其蛋白质 - 蛋白质相互作用被调节以促进病原体的细胞内存活的感染性疾病。 所描述的化合物作为核苷酸结合的竞争性抑制剂，因此也可用作靶向其他小GTP酶的支架。 一方面，本发明的治疗方法用于治疗或预防遗传性感觉神经病发作，例如Charcot-Marie-Tooth 2B型疾病。 还提供了相关的药物组合物，测定和药物筛选。
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公开(公告)号：US08765803B1
公开(公告)日：2014-07-01
申请号：US13404921
申请日：2012-02-24
申请人： Angela Wandinger-Ness , Larry Sklar , Jacob Agola , Zurab Surviladze , Jeffrey Aubé , Jennifer Golden , Chad E. Schroeder , Denise S. Simpson
发明人： Angela Wandinger-Ness , Larry Sklar , Jacob Agola , Zurab Surviladze , Jeffrey Aubé , Jennifer Golden , Chad E. Schroeder , Denise S. Simpson
CPC分类号： C07D495/04 , A61K31/381 , A61K45/06
摘要： This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.
摘要翻译： 本发明涉及化合物及其作为Rab7 GTPase的抑制剂或活化剂的用途，用于治疗或预防Rab 7 GTP酶相关疾病如神经病变，癌症，骨骼和脂质储存代谢疾病的发生。 本发明也适用于Rab7灭活或其蛋白质 - 蛋白质相互作用被调节以促进病原体的细胞内存活的感染性疾病。 所描述的化合物作为核苷酸结合的竞争性抑制剂，因此也可用作靶向其他小GTP酶的支架。 一方面，本发明的治疗方法用于治疗或预防遗传性感觉神经病发作，例如Charcot-Marie-Tooth 2B型疾病。 还提供了相关的药物组合物，测定和药物筛选。
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公开(公告)号：US20070065942A1
公开(公告)日：2007-03-22
申请号：US11469265
申请日：2006-08-31
IPC分类号： C12N5/08
CPC分类号： C12N5/0687 , C12N2502/02 , C12N2502/256
摘要： The present disclosure provides human renal stem cells. Also described are human renal stem cells isolated from the papillary region of the human kidney and methods of isolating the same. Also described are methods for culturing, characterizing, and differentiating the same, including methods for identifying human renal stem cells that are positive for Nestin and CD133, and methods for allowing the cells to differentiate into neurons.
摘要翻译： 本公开提供人肾细胞。 还描述了从人肾脏的乳头区域分离的人肾干细胞及其分离方法。 还描述了用于培养，表征和分化其的方法，包括用于鉴定对巢蛋白和CD133呈阳性的人肾干细胞的方法，以及允许细胞分化为神经元的方法。
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公开(公告)号：US07785900B1
公开(公告)日：2010-08-31
申请号：US11652432
申请日：2007-01-11
申请人： Peter C. Simons , Larry A. Sklar , Eric R. Prossnitz , Angela Wandinger-Ness , Mathewos Z. Tessema , John C. Reed , Dayong Zhai
发明人： Peter C. Simons , Larry A. Sklar , Eric R. Prossnitz , Angela Wandinger-Ness , Mathewos Z. Tessema , John C. Reed , Dayong Zhai
IPC分类号： G01N33/543 , G01N33/53
CPC分类号： G01N33/54393 , G01N33/543
摘要： The present invention relates generally to glutathione derivatized beads which are adapted for use in conjunction with glutathione-S-transferase fusion proteins (generally, GST fusion proteins, which contain a fluorescent label such as fluorescent green protein) for use in flow cytometry. The present invention also relates to methods for detecting and/or quantifying interactions between a GST fusion protein and their binding partners, in particular, labeled binding partners such as fluorescently labeled binding partners. By creating glutathione beads with an appropriate high or increased site density, disadvantages often associated with low affinity systems and quick off-rates in solution may be resolved to provide a workable system and method. Methods of identifying potential agonists, antagonists and regulator compounds of proteins fused to GST from libraries of compounds represents another aspect of the present invention.
摘要翻译： 本发明一般涉及适用于与流式细胞术中使用的谷胱甘肽-S-转移酶融合蛋白（通常为含有荧光标记如荧光绿蛋白的GST融合蛋白）结合使用的谷胱甘肽衍生化珠粒。 本发明还涉及用于检测和/或定量GST融合蛋白与其结合配偶体，特别是标记的结合配偶体如荧光标记的结合配偶体之间的相互作用的方法。 通过产生具有适当的高或增加的位点密度的谷胱甘肽珠，可以解决通常与低亲和力系统相关的缺点和解决方案中的快速关闭速率，以提供可行的系统和方法。 从化合物文库鉴定与GST融合的蛋白质的潜在激动剂，拮抗剂和调节剂化合物的方法代表本发明的另一方面。
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公开(公告)号：US07776592B2
公开(公告)日：2010-08-17
申请号：US11469265
申请日：2006-08-31
CPC分类号： C12N5/0687 , C12N2502/02 , C12N2502/256
摘要： The present disclosure provides human renal stem cells. Also described are human renal stem cells isolated from the papillary region of the human kidney and methods of isolating the same. Also described are methods for culturing, characterizing, and differentiating the same, including methods for identifying human renal stem cells that are positive for Nestin and CD133, and methods for allowing the cells to differentiate into neurons.
摘要翻译： 本公开提供人肾细胞。 还描述了从人肾脏的乳头区域分离的人肾干细胞及其分离方法。 还描述了用于培养，表征和分化其的方法，包括用于鉴定对巢蛋白和CD133呈阳性的人肾干细胞的方法，以及允许细胞分化为神经元的方法。
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