公开(公告)号：WO2016141492A1

公开(公告)日：2016-09-15

申请号：PCT/CA2016/050270

申请日：2016-03-11

申请人： UNIVERSITÉ DE MONTRÉAL ,  RSEM, LIMITED PARTNERSHIP

发明人： SAUVAGEAU, Guy ,  LAVALLÉE, Vincent-Philippe ,  LEMIEUX, Sébastien ,  HÉBERT, Josée ,  MELOCHE, Sylvain ,  BACCELLI, Irène ,  LEHNERTZ, Bernhard

IPC分类号： A61K31/519 ,  A61K31/166 ,  A61K31/4184 ,  A61P35/02 ,  C07C259/10 ,  C07D235/08 ,  C07D471/04 ,  C12Q1/68 ,  G01N33/48

CPC分类号： A61K31/166 ,  A61K31/4184 ,  A61K31/519 ,  C07C259/10 ,  C07D235/08 ,  C07D471/04 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/48

摘要： Genes exhibiting specific mutational and/or transcriptional patterns in mixed-lineage leukemia- rearranged acute myeloid leukemia (MLL leukemia) relative to other types of AMLs are disclosed. The use of these mutational and/or transcriptional patterns for the diagnosis, prognosis, characterization and/or treatment of MLL leukemia is also disclosed.

摘要翻译： 公开了相对于其他类型的AML在混合白血病重排的急性骨髓性白血病（MLL白血病）中显示特异性突变和/或转录模式的基因。 还公开了这些突变和/或转录模式用于MLL白血病的诊断，预后，表征和/或治疗的用途。

公开(公告)号：WO2018023197A1

公开(公告)日：2018-02-08

申请号：PCT/CA2017/050921

申请日：2017-08-01

申请人： UNIVERSITÉ DE MONTRÉAL

发明人： SAUVAGEAU, Guy ,  BACCELLI, Irène

IPC分类号： A61K31/422 ,  A61P35/02 ,  C07D413/12 ,  G01N33/48

摘要： A method for treating acute myeloid leukemia (AML), such as poor risk AML, by administering to a subject in need thereof an effective amount of a mitochondrial activity inhibitor, for example a class A electron transport chain (ETC) complex I inhibitor such as Mubritinib or a pharmaceutically acceptable salt thereof, is disclosed. The AML to be treated may be characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (NΚ), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

摘要翻译： 治疗急性骨髓性白血病（AML）如不良风险AML的方法，通过向有需要的受试者施用有效量的线粒体活性抑制剂，例如A类电子传递链 （ETC）复合物I抑制剂，例如Mubritinib或其药学上可接受的盐。 待治疗的AML可以通过某些特征来表征，例如一个或多个同源异形盒（HOX） - 网络基因的高水平表达，特定基因的高和/或低表达，一种或多种细胞遗传或分子风险的存在 中间细胞遗传学风险，正常核型（NK），突变NPM1，突变CEBPA，突变FLT3，突变DNMT3A，突变TET2，突变IDH1，突变IDH2，突变RUNX1，突变WT1，突变SRSF2，中等细胞遗传学风险与异常核型 实验室（abnK）），8三体（+8）和/或异常染色体（5/7）和/或高白血病干细胞（LSC）频率。

公开(公告)号：WO2019084662A1

公开(公告)日：2019-05-09

申请号：PCT/CA2018/000206

申请日：2018-11-02

申请人： UNIVERSITÉ DE MONTRÉAL

发明人： GAREAU, Yves ,  GINGRAS, Stéphane ,  CHANTIGNY, Yves ,  YANG, Gaoqiang ,  SAUVAGEAU, Guy ,  BACCELLI, Irène ,  MARINIER, Anne

IPC分类号： C07D413/12 ,  A61K31/421 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/501 ,  A61K31/506 ,  A61P35/02 ,  C07D263/32 ,  C07D263/34 ,  C07D417/12 ,  G01N33/48

摘要： Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (A/K), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.