公开(公告)号：US20160046647A1

公开(公告)日：2016-02-18

申请号：US14773686

申请日：2014-03-10

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Jolanta Grembecka ,  Tomasz Cierpicki ,  Dmitry Borkin ,  Jay Hess ,  Duxin Sun ,  Xiaoqin Li

IPC: C07D495/04

CPC classification number: C07D495/04 ,  C07D495/16 ,  C07D519/00

Abstract: The present invention relates generally to thienopyrimidine and thienopyridine class compounds and methods of use thereof. In particular embodiments, the present invention provides compositions comprising thienopyrimidine and thienopyridine class compounds and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins (e.g., for the treatment of leukemia, solid cancers and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin).

Abstract translation: 本发明一般涉及噻吩并嘧啶和噻吩并吡啶类化合物及其使用方法。 在具体实施方案中，本发明提供了包含噻吩并嘧啶和噻吩并吡啶类化合物的组合物和用于抑制menin与MLL1，MLL2和MLL-融合癌蛋白相互作用的方法（例如，用于治疗白血病，固体癌症和依赖于 MLL1，MLL2，MLL融合蛋白和/或menin的活性）。

公开(公告)号：US09862746B2

公开(公告)日：2018-01-09

申请号：US14763596

申请日：2014-02-14

Applicant: The Regents of the University of Michigan

Inventor： Zaneta Nikolovska-Coleska ,  Chenxi Shen ,  Jay Hess

IPC: A61K31/551 ,  C07D243/10 ,  A61K45/06 ,  C07K7/06 ,  G01N33/574 ,  C07K14/82 ,  A61K31/352 ,  A61K31/437 ,  A61K31/4402 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5513 ,  A61K38/08 ,  C07D213/74 ,  C07D261/20 ,  C07D311/76 ,  C07D405/04 ,  C07D409/04 ,  C07D519/00

CPC classification number: C07K7/06 ,  A61K31/352 ,  A61K31/437 ,  A61K31/4402 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5513 ,  A61K38/08 ,  A61K45/06 ,  C07D213/74 ,  C07D261/20 ,  C07D311/76 ,  C07D405/04 ,  C07D409/04 ,  C07D519/00 ,  C07K14/82 ,  C07K2319/00 ,  G01N33/57426 ,  G01N2500/02

Abstract: The present invention relates to MLL fusion proteins (e.g., AF9 and ENL), which activate target genes in part via recruitment of histone methyltransferase DOT1L. In particular, the present invention provides the AF9/ENL binding site in DOT1L and agents that block the protein-protein interactions between AF9/ENL and DOT1L, therefore inhibiting the activity of DOT1L, and inhibiting MLL-fusion protein associated leukemia.

公开(公告)号：US20160045504A1

公开(公告)日：2016-02-18

申请号：US14665600

申请日：2015-03-23

Applicant: The Regents of the University of Michigan ,  University of Virginia Patent Foundation

Inventor： Jolanta Grembecka ,  Tomasz Cierpicki ,  Jay Hess

IPC: A61K31/519 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/5377

CPC classification number: A61K31/519 ,  A61K31/5377 ,  A61K31/551 ,  A61K31/5513

Abstract: The invention relates generally to effective treatment leukemia. In particular, the present invention provides compositions and methods to inhibit the interaction of menin with MLL and MLL-fusion oncoproteins, and well as systems and methods to screen for such compositions.

Abstract translation: 本发明一般涉及有效治疗白血病。 特别地，本发明提供了抑制menin与MLL和MLL-融合癌蛋白相互作用的组合物和方法，以及筛选这些组合物的系统和方法。

公开(公告)号：US09505781B2

公开(公告)日：2016-11-29

申请号：US14773686

申请日：2014-03-10

Applicant: The Regents of the University of Michigan

Inventor： Jolanta Grembecka ,  Tomasz Cierpicki ,  Dmitry Borkin ,  Jay Hess ,  Duxin Sun ,  Xiaoqin Li

IPC: C07D495/04 ,  C07D519/00 ,  C07D495/16

CPC classification number: C07D495/04 ,  C07D495/16 ,  C07D519/00

Abstract: The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 4b: and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

公开(公告)号：US20150368300A1

公开(公告)日：2015-12-24

申请号：US14763596

申请日：2014-02-14

Applicant: The Regents of the University of Michigan

Inventor： Zaneta Nikolovska-Coleska ,  Chenxi Shen ,  Jay Hess

IPC: C07K7/06 ,  C07D405/04 ,  A61K31/5513 ,  C07D261/20 ,  A61K31/454 ,  C07D519/00 ,  A61K31/437 ,  A61K31/5377 ,  C07D311/76 ,  A61K31/352 ,  C07D213/74 ,  A61K31/4402 ,  A61K31/496 ,  C07D409/04 ,  A61K45/06 ,  A61K38/08

CPC classification number: C07K7/06 ,  A61K31/352 ,  A61K31/437 ,  A61K31/4402 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5513 ,  A61K38/08 ,  A61K45/06 ,  C07D213/74 ,  C07D261/20 ,  C07D311/76 ,  C07D405/04 ,  C07D409/04 ,  C07D519/00 ,  C07K14/82 ,  C07K2319/00 ,  G01N33/57426 ,  G01N2500/02

Abstract: The present invention relates to MLL fusion proteins (e.g., AF9 and ENL), which activate target genes in part via recruitment of histone methyltransferase DOT1L. In particular, the present invention provides the AF9/ENL binding site in DOT1L and agents that block the protein-protein interactions between AF9/ENL and DOT1L, therefore inhibiting the activity of DOT1L, and inhibiting MLL-fusion protein associated leukemia.

Abstract translation: 本发明涉及通过募集组蛋白甲基转移酶DOT1L部分激活靶基因的MLL融合蛋白（例如AF9和ENL）。 特别地，本发明提供DOT1L中的AF9 / ENL结合位点和阻断AF9 / ENL和DOT1L之间的蛋白质 - 蛋白质相互作用的试剂，从而抑制DOT1L的活性，并抑制MLL-融合蛋白相关白血病。