公开(公告)号：US20100021921A1

公开(公告)日：2010-01-28

申请号：US12545133

申请日：2009-08-21

申请人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

发明人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

IPC分类号： C12Q1/68 ,  C12N9/12 ,  C07H21/00 ,  C12N15/63 ,  C12N1/00

CPC分类号： C12N9/1205

摘要： The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, Ile313, Phe317, Met318, Met351, Glu355, Glu359, Ile360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

摘要翻译： 本发明涉及分离的多肽，其包含功能性激酶结构域，所述功能性激酶结构域包含天然人Abl激酶结构域的氨基酸序列或其基本相似的序列，其中至少一种选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，Ile313，Phe317，Met318，Met351，Glu355，Glu359，Ile360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一个氨基酸取代，所述突变的功能性激酶结构域对 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺抑制其酪氨酸激酶活性 或其盐使用这样的多肽筛选抑制这种多肽的酪氨酸激酶活性的化合物，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及使用其 核酸分子 生产这样的多肽用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。

公开(公告)号：US20050202519A1

公开(公告)日：2005-09-15

申请号：US10491603

申请日：2002-10-04

申请人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Chriatian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

发明人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Chriatian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

IPC分类号： C12N15/09 ,  C07H21/04 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/12 ,  C12Q1/48

CPC分类号： C12N9/1205

摘要： The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, Ile313, Phe317, Met318, Met351, Glu355, Glu359, Ile360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

摘要翻译： 本发明涉及分离的多肽，其包含功能性激酶结构域，所述功能性激酶结构域包含天然人Abl激酶结构域的氨基酸序列或其基本相似的序列，其中至少一种选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，Ile313，Phe317，Met318，Met351，Glu355，Glu359，Ile360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一个氨基酸取代，所述突变的功能性激酶结构域对 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺抑制其酪氨酸激酶活性 或其盐使用这样的多肽筛选抑制这种多肽的酪氨酸激酶活性的化合物，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及使用其 核酸分子 生产这样的多肽用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。

公开(公告)号：US20090117641A1

公开(公告)日：2009-05-07

申请号：US12165217

申请日：2008-06-30

申请人： Christophe Barthe ,  Susan Bradford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francios-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

发明人： Christophe Barthe ,  Susan Bradford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francios-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

IPC分类号： C12N9/12

CPC分类号： C12N9/1205

摘要： The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, Ile313, Phe317, Met318, Met351, Glu355, Glu359, Ile360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

摘要翻译： 本发明涉及分离的多肽，其包含功能性激酶结构域，所述功能性激酶结构域包含天然人Abl激酶结构域的氨基酸序列或其基本相似的序列，其中至少一种选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，Ile313，Phe317，Met318，Met351，Glu355，Glu359，Ile360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一个氨基酸取代，所述突变的功能性激酶结构域对 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺抑制其酪氨酸激酶活性 或其盐使用这样的多肽筛选抑制这种多肽的酪氨酸激酶活性的化合物，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及使用其 核酸分子 生产这样的多肽用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。