公开(公告)号：US11572369B2

公开(公告)日：2023-02-07

申请号：US17427487

申请日：2020-02-03

Applicant: UNIVERSITY OF SOUTH CAROLINA ,  SENEX BIOTECHNOLOGY, INC.

Inventor： Igor B. Roninson ,  Mengqian Chen ,  Jing Li ,  Jiaxin Liang ,  Li Zhang ,  Campbell McInnes

IPC: C07D495/02 ,  A61P35/02 ,  A61P35/04

Abstract: Disclosed herein are bicyclic pyridines, such as thienopyridine, pyrrolopyridine, furopyridine compounds, and methods for treating cancers.

公开(公告)号：US20210276956A1

公开(公告)日：2021-09-09

申请号：US17330279

申请日：2021-05-25

Applicant: University of South Carolina ,  Senex Biotechnology, Inc.

Inventor： Igor Roninson ,  Campbell McInnes ,  Mengqian Chen ,  Li Zhang ,  Jing Li

IPC: C07D215/48 ,  C07D215/233 ,  C07D215/18 ,  C07D215/42 ,  C07D215/44 ,  A61P35/00 ,  A61P35/02

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted qunioline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

公开(公告)号：US11014906B2

公开(公告)日：2021-05-25

申请号：US16547350

申请日：2019-08-21

Applicant: University of South Carolina ,  Senex Biotechnology, Inc.

Inventor： Igor Roninson ,  Campbell McInnes ,  Mengqian Chen ,  Li Zhang ,  Jing Li

IPC: C07D401/04 ,  C07D215/46 ,  C07D401/12 ,  C07D215/48

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted quinoline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

公开(公告)号：US20200062728A1

公开(公告)日：2020-02-27

申请号：US16547350

申请日：2019-08-21

Applicant: University of South Carolina ,  Senex Biotechnology, Inc.

Inventor： Igor Roninson ,  Campbell McInnes ,  Mengqian Chen ,  Li Zhang ,  Jing Li

IPC: C07D401/04 ,  C07D401/12 ,  C07D215/46

Abstract: Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted qunioline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

公开(公告)号：US09636342B2

公开(公告)日：2017-05-02

申请号：US14439127

申请日：2013-11-01

Applicant: UNIVERSITY OF SOUTH CAROLINA

Inventor： Mengqian Chen ,  Igor Roninson

IPC: A61K31/517 ,  A61K31/5377

CPC classification number: A61K31/517 ,  A61K31/5377

Abstract: The invention provides a method for treating prostate cancer in a subject comprising administering to the subject an effective amount of a selective inhibitor of one or more of CDK8 and CDK19. In some embodiments the inhibitor inhibits CDK19. In some embodiments, the inhibitor inhibits CDK8 at a Kd of lower than 200 nM and/or inhibits CDK19 at a Kd of lower than 100 nM. In some embodiments, the prostate cancer is androgen independent. In some embodiments, the prostate cancer is androgen independent due to one or more of androgen receptor gene amplification, androgen receptor gene mutation, ligand-independent transactivation of androgen receptor and activation of intracellular androgen synthesis. In some embodiments, the inhibitor inhibits increased activity of NF-κB. In some embodiments, the inhibitor does not inhibit increased basal levels of NF-κB. In some embodiments, inhibition of one or more genes by AR is not inhibited.

公开(公告)号：US20150272953A1

公开(公告)日：2015-10-01

申请号：US14439127

申请日：2013-11-01

Applicant: UNIVERSITY OF SOUTH CAROLINA

Inventor： Mengqian Chen ,  Igor Roninson

IPC: A61K31/517

CPC classification number: A61K31/517 ,  A61K31/5377

Abstract: The invention provides a method for treating prostate cancer in a subject comprising administering to the subject an effective amount of a selective inhibitor of one or more of CDK8 and CDK19. In some embodiments the inhibitor inhibits CDK19. In some embodiments, the inhibitor inhibits CDK8 at a Kd of lower than 200 nM and/or inhibits CDK19 at a Kd of lower than 100 nM. In some embodiments, the prostate cancer is androgen independent. In some embodiments, the prostate cancer is androgen independent due to one or more of androgen receptor gene amplification, androgen receptor gene mutation, ligand-independent transactivation of androgen receptor and activation of intracellular androgen synthesis. In some embodiments, the inhibitor inhibits increased activity of NF-κB. In some embodiments, the inhibitor does not inhibit increased basal levels of NF-κB. In some embodiments, inhibition of one or more genes by AR is not inhibited.

Abstract translation: 本发明提供了一种用于治疗受试者中前列腺癌的方法，其包括向受试者施用有效量的一种或多种CDK8和CDK19的选择性抑制剂。 在一些实施方案中，抑制剂抑制CDK19。 在一些实施方案中，抑制剂以低于200nM的Kd抑制CDK8和/或以低于100nM的Kd抑制CDK19。 在一些实施方案中，前列腺癌是与雄激素无关的。 在一些实施方案中，由于雄激素受体基因扩增，雄激素受体基因突变，雄激素受体的配体非依赖性反式激活和细胞内雄激素合成的激活中的一种或多种，​​前列腺癌是雄激素独立的。 在一些实施方案中，抑制剂抑制NF-κB的活性增加。 在一些实施方案中，抑制剂不抑制NF-κB的增加的基础水平。 在一些实施方案中，AR抑制一个或多个基因不被抑制。