公开(公告)号：US20180140550A1

公开(公告)日：2018-05-24

申请号：US15873400

申请日：2018-01-17

Applicant: The Regents of the University of Michigan

Inventor： Kanokwan Sansanaphongpricha ,  Hongwei Chen ,  Duxin Sun

IPC: A61K9/107 ,  A61K47/34 ,  A61K31/00 ,  A61K31/704

CPC classification number: A61K9/107 ,  A61K9/0019 ,  A61K9/5138 ,  A61K9/5146 ,  A61K31/00 ,  A61K31/704 ,  A61K47/34

Abstract: The present invention provides compositions, systems, and methods employing cleavable polymeric micelles. For example, provided herein are compositions comprising micelles that contain a hydrophobic agent (e.g., metal nanoparticles and/or therapeutic agent), where the micelles are formed from a plurality of amphiphilic polymer molecules that comprise a hydrophilic polymer and a hydrophobic polymer, where the hydrophobic polymer comprises a cleavable Furan-Maleimide adduct. Also provided herein are methods of administering such compositions to a subject and treating a localized area of the subject with a device that emits heat, NIR light, and/or alternating magnetic current such that at least some of the micelles inside the subject near the localized area are disrupted (e.g., releasing a therapeutic agent).

公开(公告)号：US09580430B2

公开(公告)日：2017-02-28

申请号：US14633360

申请日：2015-02-27

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Yujun Zhao ,  Bing Zhou ,  Angelo Aguilar ,  Liu Liu ,  Longchuan Bai ,  Donna McEachern ,  Duxin Sun ,  Bo Wen ,  Ruijuan Luo ,  Ting Zhao ,  Arul Chinnaiyan ,  Irfan A. Asangani ,  Jeanne Stuckey ,  Jennifer Lynn Meagher ,  Xu Ran ,  Yang Hu

IPC: A01N43/54 ,  A61K31/505 ,  C07D491/00 ,  C07D487/04 ,  A61K31/519 ,  C07D487/14 ,  C07D519/00

CPC classification number: C07D519/00 ,  A61K31/437 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/538 ,  C07D487/04 ,  C07D487/14

Abstract: The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, A, B1, B2, G, X1, Y1, Y2, and Y3 are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a condition or disorder responsive to inhibition of BET bromodomains. Compounds of the present disclosure are especially useful for treating cancer.

Abstract translation: 本公开提供取代的9H-嘧啶并[4,5-b]吲哚和5H-吡啶并[4,3-b]吲哚和由式I表示的相关类似物及其药学上可接受的盐，水合物和溶剂合物，其中R1a A，B1，B2，G，X1，Y1，Y2和Y3如说明书中所述。 本公开还涉及式I化合物用于治疗对抑制BET溴结构域有反应的病症或病症。 本公开的化合物特别可用于治疗癌症。

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：US09403856B2

公开(公告)日：2016-08-02

申请号：US14816191

申请日：2015-08-03

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Jianfang Chen ,  Donna McEachern ,  Longchuan Bai ,  Liu Liu ,  Duxin Sun ,  Xiaoqin Li ,  Angelo Aguilar

IPC: C07D401/12 ,  C07D403/12 ,  C07F9/6558 ,  A61K31/496 ,  A61K31/675 ,  A61K45/06 ,  A61N5/10 ,  A61K33/30

CPC classification number: C07F9/65583 ,  A61K31/675 ,  A61K33/30 ,  A61K45/06 ,  A61N5/10 ,  A61K2300/00

Abstract: Inhibitors of Bcl-2/Bcl-xL and compositions containing the same are disclosed. Methods of using the Bcl-2/Bcl-xL inhibitors in the treatment of diseases and conditions wherein inhibition of Bcl-2/Bcl-xL provides a benefit, like cancers, also are disclosed.

Abstract translation: 公开了Bcl-2 / Bcl-xL的抑制剂及其组合物。 还公开了使用Bcl-2 / Bcl-xL抑制剂治疗其中Bcl-2 / Bcl-xL的抑制提供益处的疾病和病症的方法，如癌症。

公开(公告)号：US20150336994A1

公开(公告)日：2015-11-26

申请号：US14816191

申请日：2015-08-03

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Jianfang Chen ,  Donna McEachern ,  Longchuan Bai ,  Liu Liu ,  Duxin Sun ,  Xiaoqin Li ,  Angelo Aguilar

IPC: C07F9/6558 ,  A61K45/06 ,  A61N5/10 ,  A61K31/675

CPC classification number: C07F9/65583 ,  A61K31/675 ,  A61K33/30 ,  A61K45/06 ,  A61N5/10 ,  A61K2300/00

Abstract: Inhibitors of Bcl-2/Bcl-xL and compositions containing the same are disclosed. Methods of using the Bcl-2/Bcl-xL inhibitors in the treatment of diseases and conditions wherein inhibition of Bcl-2/Bcl-xL provides a benefit, like cancers, also are disclosed.

Abstract translation: 公开了Bcl-2 / Bcl-xL的抑制剂及其组合物。 还公开了使用Bcl-2 / Bcl-xL抑制剂治疗其中Bcl-2 / Bcl-xL的抑制提供益处的疾病和病症的方法，如癌症。

公开(公告)号：US09079913B2

公开(公告)日：2015-07-14

申请号：US14485054

申请日：2014-09-12

Applicant: The Regents of the University of Michigan

Inventor： Shaomeng Wang ,  Shanghai Yu ,  Wei Sun ,  Sanjeev Kumar ,  Duxin Sun ,  Peng Zou ,  Donna McEachern ,  Yujun Zhao

IPC: C07D487/10 ,  A61K31/407 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/675 ,  A61K45/06 ,  C07D491/107 ,  C07D495/10 ,  C07D471/20 ,  C07F9/6561

CPC classification number: C07D487/10 ,  A61K31/407 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/675 ,  A61K45/06 ,  C07D471/20 ,  C07D491/107 ,  C07D495/10 ,  C07F9/6561 ,  A61K2300/00

Abstract: Provided herein are compounds, compositions, and methods in the field of medicinal chemistry. The compounds and compositions provided herein relate to spiro-oxindoles which function as antagonists of the interaction between p53 and MDM2, and their use as therapeutics for the treatment of cancer and other diseases.

Abstract translation: 本文提供了药物化学领域中的化合物，组合物和方法。 本文提供的化合物和组合物涉及用作p53和MDM2之间相互作用的拮抗剂的螺 - 羟基吲哚，以及它们作为治疗癌症和其它疾病的治疗剂的用途。

公开(公告)号：US20150065858A1

公开(公告)日：2015-03-05

申请号：US14476408

申请日：2014-09-03

Applicant: The Regents of the University of Michigan

Inventor： Hongwei Chen ,  Duxin Sun

IPC: A61K49/18 ,  A61K33/26 ,  A61B5/00 ,  G01R33/56 ,  G01R33/48 ,  A61K41/00 ,  A61N5/06

CPC classification number: A61K49/1824 ,  A61B5/0035 ,  A61B5/0075 ,  A61B5/055 ,  A61K41/0052 ,  A61K49/1827 ,  A61K49/183 ,  A61K49/1833 ,  A61K49/1851 ,  A61N5/062 ,  A61N2005/0659 ,  G01R33/4808 ,  G01R33/5601

Abstract: The present invention provides methods, compositions, systems, and kits comprising core-satellite nanocomposites useful for photothermal and/or MRI applications (e.g., tumor treatment and/or imaging). In certain embodiments, the core-satellite nanocomposites comprise: i) a core nanoparticle complex comprising a biocompatible coating surrounding a nanoparticle core, and ii) at least one satellite component attached to, or absorbed to, the biocompatible coating. In some embodiments, the nanoparticle core and satellite component are composed of near-infrared photothermal agent material and/or MRI contrast agent material. In further embodiments, the satellite component is additionally or alternatively composed of near-infrared optical dye material.

Abstract translation: 本发明提供包含可用于光热和/或MRI应用（例如肿瘤治疗和/或成像）的核心 - 卫星纳米复合材料的方法，组合物，系统和试剂盒。 在某些实施方案中，核心 - 卫星纳米复合材料包括：i）核心纳米颗粒复合物，其包含围绕纳米颗粒核心的生物相容性涂层，以及ii）附着于生物相容性涂层或吸收生物相容性涂层的至少一种卫星组分。 在一些实施例中，纳米颗粒核心和卫星部件由近红外光热剂材料和/或MRI造影剂材料组成。 在另外的实施例中，卫星组件另外地或替代地由近红外光学染料材料组成。

公开(公告)号：US20140275070A1

公开(公告)日：2014-09-18

申请号：US14203233

申请日：2014-03-10

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

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

IPC: C07D495/04 ,  C07D495/16

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 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 and MLL2 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，本发明提供包含噻吩并嘧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和MLL2或menin）。

公开(公告)号：US20140256706A1

公开(公告)日：2014-09-11

申请号：US14204076

申请日：2014-03-11

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Xu Ran ,  Yujun Zhao ,  Chao-Yie Yang ,  Liu Liu ,  Longchuan Bai ,  Donna McEachern ,  Jeanne Stuckey ,  Jennifer Lynn Meagher ,  Duxin Sun ,  Xiaoqin Li ,  Bing Zhou ,  Hacer Karatas ,  Ruijuan Luo ,  Arul Chinnaiyan ,  Irfan A. Asangani

IPC: A61K31/5377 ,  A61K31/437 ,  A61K45/06 ,  C07D471/04 ,  C07D491/056 ,  A61K31/519 ,  C07D487/04

CPC classification number: A61K45/06 ,  C07D471/04 ,  C07D487/04 ,  C07D491/056

Abstract: Inhibitors of BET bromodomains and compositions containing the same are disclosed. Methods of using the BET bromodomain inhibitors in the treatment of diseases and conditions wherein inhibition of BET bromodomain provides a benefit, like cancers, also are disclosed.

Abstract translation: 公开了BET溴结构域的抑制剂和含有它们的组合物。 还公开了使用BET溴域结构域抑制剂治疗其中抑制BET溴结构域提供益处的疾病和病症的方法，如癌症。

公开(公告)号：US20140199234A1

公开(公告)日：2014-07-17

申请号：US14155809

申请日：2014-01-15

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Jianfang Chen ,  Donna McEachern ,  Longchuan Bai ,  Liu Liu ,  Duxin Sun ,  Xiaoqin Li ,  Angelo Aguilar

IPC: C07F9/6558 ,  A61K45/06 ,  A61K31/675

CPC classification number: C07F9/65583 ,  A61K31/675 ,  A61K33/30 ,  A61K45/06 ,  A61N5/10 ,  A61K2300/00

Abstract: Inhibitors of Bcl-2/Bcl-xL and compositions containing the same are disclosed. Methods of using the Bcl-2/Bcl-xL inhibitors in the treatment of diseases and conditions wherein inhibition of Bcl-2/Bcl-xL provides a benefit, like cancers, also are disclosed.

Abstract translation: 公开了Bcl-2 / Bcl-xL的抑制剂及其组合物。 还公开了使用Bcl-2 / Bcl-xL抑制剂治疗其中Bcl-2 / Bcl-xL的抑制提供益处的疾病和病症的方法，如癌症。