公开(公告)号：US08394806B2

公开(公告)日：2013-03-12

申请号：US13183348

申请日：2011-07-14

申请人： Christopher John Burns ,  Andrew Frederick Wilks ,  Michael Francis Harte ,  Harrison Sikanyika ,  Emmanuelle Fantino

发明人： Christopher John Burns ,  Andrew Frederick Wilks ,  Michael Francis Harte ,  Harrison Sikanyika ,  Emmanuelle Fantino

IPC分类号： A61K31/4965

CPC分类号： C07D253/07 ,  C07D213/74 ,  C07D239/42 ,  C07D241/20 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

摘要： Compounds of general formula (I), (II), (III) and (V) are described for use in modulating microtubule polymerisation and in the treatment of associated disease states. Use of compounds (I), (III) and (V) in the treatment of kinase-associated disease states is also described. Further described are novel compounds of formula (II), (III) and (V).

摘要翻译： 描述了通式（I），（II），（III）和（V）的化合物用于调节微管聚合和治疗相关疾病状态。 还描述了化合物（I），（III）和（V）在激酶相关疾病状态的治疗中的用途。 进一步描述的是式（II），（III）和（V）的新化合物。

公开(公告)号：US07981900B2

公开(公告)日：2011-07-19

申请号：US10581534

申请日：2004-12-03

申请人： Christopher John Burns ,  Andrew Frederick Wilks ,  Michael Francis Harte ,  Harrison Sikanyika ,  Emmanuelle Fantino

发明人： Christopher John Burns ,  Andrew Frederick Wilks ,  Michael Francis Harte ,  Harrison Sikanyika ,  Emmanuelle Fantino

IPC分类号： A01N43/54

CPC分类号： C07D253/07 ,  C07D213/74 ,  C07D239/42 ,  C07D241/20 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

摘要： Compounds of general formula (I), (II) (III) and (V) are described for use in modulating microtubule polymerisation and in the treatment of associated disease states. Use of compounds (I), (III) and (V) in the treatment of kinase-associated disease states is also described. Further described are novel compounds of formula (II), (III) and (V).

摘要翻译： 描述了通式（I），（II）（III）和（V）的化合物用于调节微管聚合和治疗相关疾病状态。 还描述了化合物（I），（III）和（V）在激酶相关疾病状态的治疗中的用途。 进一步描述的是式（II），（III）和（V）的新化合物。

公开(公告)号：US20070136005A1

公开(公告)日：2007-06-14

申请号：US11650004

申请日：2007-01-04

申请人： Andrew Wilks ,  Christopher Burns ,  Emmanuelle Fantino ,  Isabelle Lucet ,  Jamie Rossjohn ,  Michelle Styles

发明人： Andrew Wilks ,  Christopher Burns ,  Emmanuelle Fantino ,  Isabelle Lucet ,  Jamie Rossjohn ,  Michelle Styles

IPC分类号： G06F19/00

CPC分类号： C12N9/1205 ,  C07K2299/00 ,  Y02A90/26

摘要： The present invention relates to X-ray crystallography studies of a JAK2 kinase domain. More particularly, it relates to the crystal structure of a JAK2 kinase domain bound to an inhibitor. The invention further relates to the use of the crystal and related structural information to select and screen for compounds that interact with JAK2 and related proteins and to compounds that could be used for the treatment of diseases mediated by inappropriate JAK2 activity.

公开(公告)号：US20070129896A1

公开(公告)日：2007-06-07

申请号：US11650063

申请日：2007-01-04

申请人： Andrew Wilks ,  Christopher Burns ,  Emmanuelle Fantino ,  Isabelle Lucet ,  Jamie Rossjohn ,  Michelle Styles

发明人： Andrew Wilks ,  Christopher Burns ,  Emmanuelle Fantino ,  Isabelle Lucet ,  Jamie Rossjohn ,  Michelle Styles

IPC分类号： G06F19/00

CPC分类号： C12N9/1205 ,  C07K2299/00 ,  Y02A90/26

摘要： The present invention relates to X-ray crystallography studies of a JAK2 kinase domain. More particularly, it relates to the crystal structure of a JAK2 kinase domain bound to an inhibitor. The invention further relates to the use of the crystal and related structural information to select and screen for compounds that interact with JAK2 and related proteins and to compounds that could be used for the treatment of diseases mediated by inappropriate JAK2 activity.

公开(公告)号：US07378496B2

公开(公告)日：2008-05-27

申请号：US10722189

申请日：2003-11-24

申请人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

发明人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

IPC分类号： C07K14/705

CPC分类号： C07K14/705 ,  A61K38/00 ,  A61K48/00

摘要： The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KCNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

摘要翻译： 本发明是基于在神经细胞，骨骼肌，心脏和淋巴细胞中表达的人小电导钙激活钾通道3型（hKCa3 / KCNN3）基因的发现和克隆。 hKCa3 / KCNN3基因或其蛋白质产物的改变可能增加对精神分裂症和/或双相情感障碍的易感性。 hKCa3 / KCNN3可能参与神经精神，神经，神经肌肉和免疫疾病。 提供了大量纯化的hKCa3 / KCNN3多肽和多核苷酸。 还公开了与hKCa3 / KCNN3多肽结合的抗体。 提供了鉴定影响hKCa3 / KCNN3多核苷酸或多肽的化合物的方法。 还提供了用于诊断和确定具有hKCa3 / KCNN3相关病症或具有hKCa3 / KCNN3相关病症风险的受试者的预后和治疗方案的方法。 还提供了通过施用治疗有效量的编码SEQ ID NO：2的多核苷酸治疗患有或具有hKCa3 / KCNN3相关病症风险的受试者的方法。 提供了将hKCa3 / KCNN3给予治疗有效量的hKCa3 / KCNN3多肽的患者的制剂。 提供了可用于检测来自具有hKCa3 / KCNN3相关病症的受试者的样品中hKCa3 / KCNN3多肽或多核苷酸的存在的试剂盒。 还描述了具有编码hKCa3 / KCNN3的转基因的转基因非人动物。

公开(公告)号：US20070032411A1

公开(公告)日：2007-02-08

申请号：US11544834

申请日：2006-10-05

申请人： Andrew Wilks ,  Julie Atkin ,  Emmanuelle Fantino

发明人： Andrew Wilks ,  Julie Atkin ,  Emmanuelle Fantino

IPC分类号： A61K38/12 ,  C07K7/64

CPC分类号： C12N9/1205 ,  A61K38/00 ,  C07K14/71 ,  C12Q1/485 ,  G01N2333/9121 ,  G01N2500/00

摘要： The present invention provides a method of selecting or designing a compound for the ability to regulate JAK activity. The method comprises assessing the ability of the compound to modulate the interaction of the pseudo-substrate loop (PSL) with the kinase like domain (KLD) of JAK. In addition the present invention provides compounds which inhibit JAK and methods of treatment of JAK-associated disease states.

摘要翻译： 本发明提供了选择或设计化合物以调节JAK活性的能力的方法。 该方法包括评估化合物调节假底物环（PSL）与JAK的激酶样结构域（KLD）的相互作用的能力。 此外，本发明提供抑制JAK的化合物和治疗JAK相关疾病状态的方法。

公开(公告)号：US06653100B1

公开(公告)日：2003-11-25

申请号：US09565590

申请日：2000-05-04

申请人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

发明人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

IPC分类号： C12N1512

CPC分类号： C07K14/705 ,  A61K38/00 ,  A61K48/00

摘要： The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KCNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

摘要翻译： 本发明是基于在神经细胞，骨骼肌，心脏和淋巴细胞中表达的人小电导钙激活钾通道3型（hKCa3 / KCNN3）基因的发现和克隆。 hKCa3 / KCNN3基因或其蛋白质产物的改变可能增加对精神分裂症和/或双相情感障碍的易感性。 hKCa3 / KCNN3可能参与神经精神，神经，神经肌肉和免疫疾病。 提供了大量纯化的hKCa3 / KCNN3多肽和多核苷酸。 还公开了与hKCa3 / KCNN3多肽结合的抗体。 提供了鉴定影响hKCa3 / KCNN3多核苷酸或多肽的化合物的方法。 还提供了用于诊断和确定具有hKCa3 / KCNN3相关病症或具有hKCa3 / KCNN3相关病症风险的受试者的预后和治疗方案的方法。 还提供了通过施用治疗有效量的编码SEQ ID NO：2的多核苷酸治疗患有或具有hKCa3 / KCNN3相关病症风险的受试者的方法。 提供了将hKCa3 / KCNN3给予治疗有效量的hKCa3 / KCNN3多肽的患者的制剂。 提供了可用于检测来自具有hKCa3 / KCNN3相关病症的受试者的样品中hKCa3 / KCNN3多肽或多核苷酸的存在的试剂盒。 还描述了具有编码hKCa3 / KCNN3的转基因的转基因非人动物。

公开(公告)号：US07795206B2

公开(公告)日：2010-09-14

申请号：US11544834

申请日：2006-10-05

申请人： Andrew Frederick Wilks ,  Julie Atkin ,  Emmanuelle Fantino

发明人： Andrew Frederick Wilks ,  Julie Atkin ,  Emmanuelle Fantino

IPC分类号： A61K38/00 ,  A61K38/04

CPC分类号： C12N9/1205 ,  A61K38/00 ,  C07K14/71 ,  C12Q1/485 ,  G01N2333/9121 ,  G01N2500/00

摘要： The present invention provides a method of selecting or designing a compound for the ability to regulate JAK activity. The method comprises assessing the ability of the compound to modulate the interaction of the pseudo-substrate loop (PSL) with the kinase like domain (KLD) of JAK. In addition the present invention provides compounds which inhibit JAK and methods of treatment of JAK-associated disease states.

摘要翻译： 本发明提供了选择或设计化合物以调节JAK活性的能力的方法。 该方法包括评估化合物调节假底物环（PSL）与JAK的激酶样结构域（KLD）的相互作用的能力。 此外，本发明提供抑制JAK的化合物和治疗JAK相关疾病状态的方法。

公开(公告)号：US07593820B2

公开(公告)日：2009-09-22

申请号：US11248478

申请日：2005-10-11

申请人： Andrew Frederick Wilks ,  Christopher John Burns ,  Emmanuelle Fantino ,  Isabelle Lucet ,  Jamie Rossjohn ,  Michelle Leanne Styles

发明人： Andrew Frederick Wilks ,  Christopher John Burns ,  Emmanuelle Fantino ,  Isabelle Lucet ,  Jamie Rossjohn ,  Michelle Leanne Styles

IPC分类号： G01N31/00 ,  C12N9/12 ,  G06G7/58

CPC分类号： C07D491/04 ,  C07D471/04 ,  C07K2299/00 ,  C12N9/1205 ,  Y02A90/26

摘要： The present invention relates to X-ray crystallography studies of a human Janus Kinase 2 (JAK2) domain. More particularly, it relates to the crystal structure of a JAK2 kinase domain bound to a inhibitor. The invention further relates to the use of the crystal and related structural information to select and screen for compounds that interact with JAK2 and related proteins and to compounds that could be used for the treatment of diseases mediated by inappropriate JAK2 activity.

摘要翻译： 本发明涉及人类Janus Kinase 2（JAK2）结构域的X射线晶体学研究。 更具体地，涉及与抑制剂结合的JAK2激酶结构域的晶体结构。 本发明还涉及晶体和相关结构信息用于选择和筛选与JAK2和相关蛋白相互作用的化合物以及可用于治疗由不适当的JAK2活性介导的疾病的化合物。

公开(公告)号：US20080194583A1

公开(公告)日：2008-08-14

申请号：US10581534

申请日：2004-12-03

申请人： Christopher John Burns ,  Andrew Frederick Wilks ,  Michael Francis Harte ,  Harrison Sikanyika ,  Emmanuelle Fantino ,  Collette Gloria Kewdale

发明人： Christopher John Burns ,  Andrew Frederick Wilks ,  Michael Francis Harte ,  Harrison Sikanyika ,  Emmanuelle Fantino ,  Collette Gloria Kewdale

IPC分类号： A61K31/497 ,  A61K31/4965 ,  C07D413/12 ,  C07D401/12 ,  C07D253/00 ,  C07D241/20 ,  A61P29/00 ,  A61P35/00 ,  A61P31/00

CPC分类号： C07D253/07 ,  C07D213/74 ,  C07D239/42 ,  C07D241/20 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

摘要： Compounds of general formula (I), (II) (III) and (V) are described for use in modulating microtubule polymerisation and in the treatment of associated disease states. Use of compounds (I), (III) and (V) in the treatment of kinase-associated disease states is also described. Further described are novel compounds of formula (II), (III) and (V).

摘要翻译： 描述了通式（I），（II）（III）和（V）的化合物用于调节微管聚合和治疗相关疾病状态。 还描述了化合物（I），（III）和（V）在激酶相关疾病状态的治疗中的用途。 进一步描述的是式（II），（III）和（V）的新化合物。