公开(公告)号：US08815927B2

公开(公告)日：2014-08-26

申请号：US13503366

申请日：2010-10-20

Applicant: Shaomeng Wang ,  Haiying Sun

Inventor： Shaomeng Wang ,  Haiying Sun

IPC: C07D487/04 ,  C07D403/14 ,  C07D245/04 ,  C07D519/00

CPC classification number: C07D519/00 ,  C07D487/04

Abstract: The invention relates to diazo bicyclic Smac mimetics that are tethered through a covalent linker to give a bivalent species. Bivalent diazo bicyclic Smac mimetics function as inhibitors of Inhibitor of Apoptosis Proteins (IAPs). The invention also relates to the use of bivalent diazo bicyclic Smac mimetics for inducing or sensitizing cells to the induction of apoptotic cell death. Thus, compounds of the invention are useful in the treatment, amelioration, or prevention of hyperproliferative diseases such as cancer.

Abstract translation: 本发明涉及通过共价接头连接以产生二价物质的重氮二环Smac模拟物。 二价重氮双环Smac模拟物作为细胞凋亡蛋白抑制剂（IAP）的抑制剂起作用。 本发明还涉及二价重氮二环Smac模拟物用于诱导或致敏细胞诱导凋亡细胞死亡的用途。 因此，本发明的化合物可用于治疗，改善或预防过度增殖性疾病如癌症。

公开(公告)号：US08445473B2

公开(公告)日：2013-05-21

申请号：US12937114

申请日：2009-04-13

Applicant: Shaomeng Wang ,  Haiying Sun ,  Zaneta Nikolovska-Coleska

Inventor： Shaomeng Wang ,  Haiying Sun ,  Zaneta Nikolovska-Coleska

IPC: C07D403/04 ,  C07D403/02 ,  C07D235/06

CPC classification number: C07D487/04

Abstract: The invention relates to heteroaryl-substituted bicyclic mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Abstract translation: 本发明涉及作为细胞凋亡蛋白抑制剂抑制剂的Smac的杂芳基取代的双环模拟物。 本发明还涉及这些模拟物用于诱导凋亡性细胞死亡和使细胞对细胞凋亡诱导剂敏感的用途。

公开(公告)号：US20120302629A1

公开(公告)日：2012-11-29

申请号：US13388610

申请日：2010-07-28

Applicant: Shaomeng Wang ,  Feng Jiang ,  Jianting Long ,  Longchuan Bai

Inventor： Shaomeng Wang ,  Feng Jiang ,  Jianting Long ,  Longchuan Bai

IPC: A61K31/11 ,  C12Q1/68 ,  A61P35/00 ,  A61K31/337 ,  A61P29/00 ,  A61P31/00 ,  A61P7/00 ,  A61P35/02 ,  G01N33/574 ,  A61P37/00

CPC classification number: G01N33/57434 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N2800/52

Abstract: The present invention provides a biomarker for selecting a patient for treatment with gossypol, wherein the biomarker comprises an elevated expression level of c-Myc, Mcl-1, or combination thereof, relative to the normal expression level of c-Myc, Mcl-1, or combination thereof. The present invention also provides methods for targeting patients for treatment with gossypol, wherein the patient has a disease, condition, or disorder that overexpresses c-Myc, Mcl-1, or combination thereof. The present invention also provides methods for treating or ameliorating a disease, condition, or disorder in a patient comprising determining the expression level of c-Myc, Mcl-1, or combination thereof in the patient and administering gossypol to the patient. In certain embodiments of the invention, the disease is cancer, and the cancer cells show elevated expression levels of c-Myc compared to non-cancerous cells. The invention also provides methods for overcoming Mcl-1-mediated chemoresistance comprising administering gossypol to a patient in need thereof.

Abstract translation: 本发明提供了一种用于选择用棉酚处理的患者的生物标志物，其中相对于c-Myc，Mcl-1的正常表达水平，生物标志物包含c-Myc，Mcl-1或其组合的升高的表达水平 ，或其组合。 本发明还提供了靶向患者用棉酚治疗的方法，其中患者具有过表达c-Myc，Mcl-1或其组合的疾病，病症或病症。 本发明还提供了用于治疗或改善患者疾病，病症或障碍的方法，包括确定患者中c-Myc，Mcl-1或其组合的表达水平，并向患者施用棉酚。 在本发明的某些实施方案中，该疾病是癌症，与非癌细胞相比，癌细胞表现出c-Myc的升高的表达水平。 本发明还提供克服Mcl-1介导的化学耐药性的方法，包括向有需要的患者施用棉酚。

公开(公告)号：US08283368B2

公开(公告)日：2012-10-09

申请号：US13060306

申请日：2009-08-27

Applicant: Shaomeng Wang ,  Jianyong Chen ,  Gregory Collins ,  James H. Woods ,  Beth Levant

Inventor： Shaomeng Wang ,  Jianyong Chen ,  Gregory Collins ,  James H. Woods ,  Beth Levant

IPC: A01N43/78 ,  A61K31/425

CPC classification number: C07D277/82 ,  C07D417/12

Abstract: Potent and selective ligands for the dopamine 3 (D3) receptor are disclosed. The D3 receptor ligands have a structural formula (I) wherein X is C═O or SO2, R1 is C1-6 alkyl, R2 is aryl, heteroaryl, aryl, —(CH2)1-3aryl, or —(CH2)1-3heteroaryl, and n is 0 or 1. Methods of using the D3 receptor ligands in the treatment of diseases and conditions wherein modulation of the D3 receptor provides a benefit also are disclosed.

Abstract translation: 公开了多巴胺3（D3）受体的有效和选择性配体。 D3受体配体具有结构式（I），其中X为C = O或SO 2，R 1为C 1-6烷基，R 2为芳基，杂芳基，芳基， - （CH 2）1-3芳基或 - （CH 2） 3杂芳基，n为0或1.D3受体配体在治疗其中D3受体的调节提供益处的疾病和病症方面也被公开。

公开(公告)号：US08202902B2

公开(公告)日：2012-06-19

申请号：US12270374

申请日：2008-11-13

Applicant: Shaomeng Wang ,  Haiying Sun ,  Dongguang Qin ,  Zaneta Nikolovska-Coleska ,  Jianfeng Lu ,  Su Qiu ,  Yuefeng Peng ,  Qian Cai

Inventor： Shaomeng Wang ,  Haiying Sun ,  Dongguang Qin ,  Zaneta Nikolovska-Coleska ,  Jianfeng Lu ,  Su Qiu ,  Yuefeng Peng ,  Qian Cai

IPC: A01N47/10 ,  A61K31/27 ,  C07D225/00

CPC classification number: A61K38/191 ,  C07D487/04 ,  C07D519/00

Abstract: The invention relates to bivalent mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Abstract translation: 本发明涉及Smac的二价模拟物，其作为细胞凋亡蛋白抑制剂的抑制剂。 本发明还涉及这些模拟物用于诱导凋亡性细胞死亡和使细胞对细胞凋亡诱导剂敏感的用途。

公开(公告)号：US20110319362A1

公开(公告)日：2011-12-29

申请号：US13128941

申请日：2009-12-07

Applicant: Shaomeng Wang ,  Jianyong Chen ,  Cindy Gomez ,  Longchuan Bai ,  Zaneta Nikolovska-Coleska ,  Yu-Jun Zhao

Inventor： Shaomeng Wang ,  Jianyong Chen ,  Cindy Gomez ,  Longchuan Bai ,  Zaneta Nikolovska-Coleska ,  Yu-Jun Zhao

IPC: A61K31/675 ,  C07D487/04 ,  A61P35/00 ,  A61K31/407 ,  A61K31/4178 ,  C07F9/6561 ,  C07D495/04

CPC classification number: C07D403/12 ,  A61K31/41 ,  C07D487/04

Abstract: Inhibitors of STAT3 are disclosed. Methods of using the STAT3 inhibitors in the treatment of diseases and conditions wherein inhibition of STAT3 provides a benefit, like cancers, also are disclosed.

Abstract translation: 公开了STAT3的抑制剂。 还公开了使用STAT3抑制剂治疗其中抑制STAT3提供益处的疾病和病症的方法，如癌症。

公开(公告)号：US20110312997A1

公开(公告)日：2011-12-22

申请号：US13160086

申请日：2011-06-14

Applicant: Shaomeng Wang ,  Hacer Karatas ,  Yali Dou ,  Elizabeth Townsend ,  Denzil Bernard

Inventor： Shaomeng Wang ,  Hacer Karatas ,  Yali Dou ,  Elizabeth Townsend ,  Denzil Bernard

IPC: A61K31/445 ,  A61K31/165 ,  A61P35/00 ,  A61K31/166 ,  A61K31/4164 ,  A61P35/02 ,  A61K31/16 ,  A61K31/167

CPC classification number: A61K31/16 ,  A61K31/165 ,  A61K31/166 ,  A61K31/167 ,  A61K31/4164 ,  A61K31/445

Abstract: Peptidomimetics that inhibit the interaction between MLL1 and WDR5 are disclosed. Methods of inhibiting MLL1 activity and methods of treating cancers also are disclosed.

Abstract translation: 公开了抑制MLL1和WDR5之间相互作用的肽模拟物。 还公开了抑制MLL1活性的方法和治疗癌症的方法。

公开(公告)号：US20110251252A1

公开(公告)日：2011-10-13

申请号：US13082163

申请日：2011-04-07

Applicant: Shaomeng Wang ,  Sami Malek ,  Jianting Long ,  Peter Ouillette

Inventor： Shaomeng Wang ,  Sami Malek ,  Jianting Long ,  Peter Ouillette

IPC: A61K31/407 ,  A61P35/02 ,  C12Q1/02

CPC classification number: A61K31/407 ,  G01N33/57426

Abstract: Provided herein are methods for selecting and treating a subject with leukemia, wherein the subject is selected for treatment and is treated with an MDM2 inhibitor because said subject's cells contain an FLT3-ITD mutation.

Abstract translation: 本文提供了用于选择和治疗患有白血病的受试者的方法，其中所述受试者被选择用于治疗，并且由于所述受试者的细胞含有FLT3-ITD突变而用MDM2抑制剂治疗。

公开(公告)号：US07960372B2

公开(公告)日：2011-06-14

申请号：US11800220

申请日：2007-05-04

Applicant: Shaomeng Wang ,  Haiying Sun ,  Dongguang Qin ,  Zaneta Nikolovska-Coleska ,  Jianfeng Lu ,  Su Qiu ,  Yuefeng Peng ,  Qian Cai

Inventor： Shaomeng Wang ,  Haiying Sun ,  Dongguang Qin ,  Zaneta Nikolovska-Coleska ,  Jianfeng Lu ,  Su Qiu ,  Yuefeng Peng ,  Qian Cai

IPC: A61K31/545 ,  C07D225/00 ,  C07D403/00

CPC classification number: C07D519/00 ,  A61K38/191 ,  C07D487/04

Abstract: The invention relates to bivalent mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Abstract translation: 本发明涉及Smac的二价模拟物，其作为细胞凋亡蛋白抑制剂的抑制剂。 本发明还涉及这些模拟物用于诱导凋亡性细胞死亡和使细胞对细胞凋亡诱导剂敏感的用途。

公开(公告)号：US07910621B2

公开(公告)日：2011-03-22

申请号：US10594200

申请日：2005-03-22

Applicant: Jianyong Chen ,  Zaneta Nikolovska-Coleska ,  Dajun Yang ,  Shaomeng Wang ,  Haiying Sun ,  Liang Xu ,  Zengjian Hu

Inventor： Jianyong Chen ,  Zaneta Nikolovska-Coleska ,  Dajun Yang ,  Shaomeng Wang ,  Haiying Sun ,  Liang Xu ,  Zengjian Hu

IPC: A61K31/352 ,  C07D311/30

CPC classification number: C07C235/84 ,  C07C50/28 ,  C07C50/30 ,  C07D311/30

Abstract: The present invention relates to naturally occurring and chemically synthesized small molecule antagonists of XIAP family proteins. In particular, the present invention provides embelin and other XIAP inhibitors and methods of using these compounds as antagonists of the anti-apoptotic effects of XIAP family member proteins. The present invention also provides methods for treating diseases and pathologies (e.g., neoplastic diseases).

Abstract translation: 本发明涉及XIAP家族蛋白质的天然存在和化学合成的小分子拮抗剂。 特别地，本发明提供了塞林和其他XIAP抑制剂以及使用这些化合物作为XIAP家族蛋白的抗凋亡作用的拮抗剂的方法。 本发明还提供了治疗疾病和病理（例如肿瘤性疾病）的方法。