公开(公告)号：US09717709B2

公开(公告)日：2017-08-01

申请号：US15269584

申请日：2016-09-19

Applicant: Duke University ,  Chaperone Therapeutics, Inc.

Inventor： Dennis J. Thiele ,  Daniel W. Neef ,  Jose S. Mendoza

IPC: C07D231/10 ,  C07D409/04 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/426 ,  A61K45/06 ,  C07D231/40 ,  C07D277/42 ,  C07D277/60 ,  C07K14/47 ,  C07C211/01 ,  C07D231/38 ,  C07D277/38 ,  C07D405/14 ,  C07D413/12 ,  C07C211/29 ,  C07D277/46

CPC classification number: C07D231/40 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/426 ,  A61K45/06 ,  C07C211/01 ,  C07C211/29 ,  C07D231/38 ,  C07D277/38 ,  C07D277/42 ,  C07D277/46 ,  C07D277/60 ,  C07D405/14 ,  C07D409/04 ,  C07D413/12 ,  C07K14/47 ,  A61K2300/00

Abstract: The present invention relates to HSF activating compounds, methods for their discovery, and their research and therapeutic uses, as well as pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, mixtures (including both R and S enantiomeric forms and racemic mixtures thereof), and pharmaceutical Formulations thereof. In particular, the present invention provides compounds capable of facilitating HSF1 homotrimerization, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with irregular HSF1 activity.

公开(公告)号：US20170037471A1

公开(公告)日：2017-02-09

申请号：US15106873

申请日：2014-12-23

Applicant: Duke University

Inventor： Dennis J. Thiele ,  Byung-Eun Kim

IPC: C12Q1/68 ,  A61K33/34

CPC classification number: C12Q1/6883 ,  A61K33/34 ,  C12Q2600/118 ,  C12Q2600/156

Abstract: Described are methods and materials for diagnosing a subject's predisposition for cardiovascular disease by detecting a copper deficiency genetic marker, as well as methods of alleviating Cu transport impairment. Specifically, the Cu deficiency genetic marker may be within the gene encoding a transmembrane Cu transporter protein (Ctri) or its regulatory sequences.

Abstract translation: 描述了通过检测铜缺乏遗传标记来诊断受试者心血管疾病倾向的方法和材料，以及减轻铜转运损伤的方法。 具体地说，Cu缺陷遗传标记可能在编码跨膜Cu转运蛋白（Ctri）或其调控序列的基因内。

公开(公告)号：US20160220592A1

公开(公告)日：2016-08-04

申请号：US15094349

申请日：2016-04-08

Applicant: Duke University

Inventor： Katherine J. Franz ,  Dennis J. Thiele ,  Marian Helsel ,  Richard Festa

IPC: A61K31/69

CPC classification number: A61K31/69 ,  A61K31/40 ,  A61K31/435 ,  Y02A50/473

Abstract: The present disclosure provides methods of treating (including ameliorating and/or preventing) pathogenic infections by administering a therapeutically effective amount of a prochelator. The present disclosure further provides pharmaceutical compositions and a kit comprising the prochelator therein.

Abstract translation: 本公开提供了通过施用治疗有效量的制成者来治疗（包括改善和/或预防）致病性感染的方法。 本公开进一步提供药物组合物和其中包含其中的代理商的试剂盒。

公开(公告)号：US20240409504A1

公开(公告)日：2024-12-12

申请号：US18812888

申请日：2024-08-22

Applicant: Duke University

Inventor： Dennis J. Thiele ,  Bushu Dong ,  Alexander M. Jaeger ,  Philip F. Hughes ,  Timothy Haystead ,  Jiyong Hong

IPC: C07C275/30 ,  A61P35/00 ,  C07C211/40 ,  C07C255/60 ,  C07C275/28 ,  C07C275/34 ,  C07C275/40 ,  C07C275/42 ,  C07C279/18 ,  C07C279/28 ,  C07C281/06 ,  C07C311/46 ,  C07C317/36 ,  C07C317/42 ,  C07D213/40 ,  C07D213/75 ,  C07D223/04 ,  C07D229/02 ,  C07D231/56 ,  C07D233/64 ,  C07D241/24 ,  C07D249/14 ,  C07D271/12 ,  C07D285/10 ,  C07D317/66 ,  C07D333/20 ,  C07D333/36 ,  C07D333/72 ,  C07D405/04 ,  C07D405/12 ,  C07D417/12

Abstract: This disclosure relates to compounds, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases related to Heat Shock Transcription Factor 1 (HSF1) activity and/or function. More particularly, this disclosure relates to methods of inhibiting HSF1 activity with these compounds and pharmaceutical compositions thereof, and methods of treating diseases associated with HSF1 activity and/or function, such as cancer.

公开(公告)号：US20210187013A1

公开(公告)日：2021-06-24

申请号：US17144967

申请日：2021-01-08

Applicant: DUKE UNIVERSITY

Inventor： Chris M. Counter ,  Donita C. Brady ,  Michelle L. Turski ,  Dennis J. Thiele

IPC: A61K33/24 ,  A61K45/06 ,  A61K33/30 ,  A61K31/095 ,  A61K31/519 ,  A61K31/275 ,  A61K31/4523 ,  A61K31/132 ,  A61K31/4745 ,  A61K31/198 ,  A61K31/18 ,  A61K31/416

Abstract: The present disclosure provides methods of treating and/or preventing cancer in a subject comprising administering to the subject a copper-reduced diet by itself or as a supplement along with a regular diet to create a copper-reduced melieu, maintain a reduced-copper melieu, or both, thereby treating and/or preventing the development of the cancer. Methods also comprise further adding a copper chelator, MEK inhibitor, or combinations thereof.

公开(公告)号：US20170000768A1

公开(公告)日：2017-01-05

申请号：US15269584

申请日：2016-09-19

Applicant: Duke University ,  Chaperone Therapeutics, Inc.

Inventor： Dennis J. Thiele ,  Daniel W. Neef ,  Jose S. Mendoza

IPC: A61K31/415 ,  A61K31/426 ,  A61K31/4155

CPC classification number: C07D231/40 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/426 ,  A61K45/06 ,  C07C211/01 ,  C07C211/29 ,  C07D231/38 ,  C07D277/38 ,  C07D277/42 ,  C07D277/46 ,  C07D277/60 ,  C07D405/14 ,  C07D409/04 ,  C07D413/12 ,  C07K14/47 ,  A61K2300/00

Abstract: The present invention relates to HSF activating compounds, methods for their discovery, and their research and therapeutic uses, as well as pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, mixtures (including both R and S enantiomeric forms and racemic mixtures thereof), and pharmaceutical Formulations thereof. In particular, the present invention provides compounds capable of facilitating HSF1 homotrimerization, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with irregular HSF1 activity.

Abstract translation: 本发明涉及HSF活化化合物，其发现方法及其研究和治疗用途，以及其药学上可接受的盐，溶剂合物，螯合物，非共价复合物，前药，混合物（包括R和S对映体形式和外消旋 其混合物）及其药物制剂。 特别地，本发明提供能够促进HSF1同源三聚化的化合物，以及使用这些化合物作为治疗剂来治疗与不规则HSF1活性相关的许多病症的方法。

公开(公告)号：US09526740B2

公开(公告)日：2016-12-27

申请号：US15094349

申请日：2016-04-08

Applicant: Duke University

Inventor： Katherine J. Franz ,  Dennis J. Thiele ,  Marian Helsel ,  Richard Festa

IPC: A61K31/69 ,  A61K31/40 ,  A61K31/435

CPC classification number: A61K31/69 ,  A61K31/40 ,  A61K31/435 ,  Y02A50/473

Abstract: The present disclosure provides methods of treating (including ameliorating and/or preventing) pathogenic infections by administering a therapeutically effective amount of a prochelator. The present disclosure further provides pharmaceutical compositions and a kit comprising the prochelator therein.

公开(公告)号：US20160221958A1

公开(公告)日：2016-08-04

申请号：US15131938

申请日：2016-04-18

Applicant: DUKE UNIVERSITY ,  CHAPERONE THERAPEUTICS, INC

Inventor： Dennis J. Thiele ,  Daniel W. Neef ,  Jose Serafin Mendoza

IPC: C07D231/40 ,  C07D409/04 ,  C07C211/29 ,  C07D277/46 ,  C07D277/60 ,  C07D413/12 ,  C07D405/14 ,  C07D277/42

CPC classification number: C07D231/40 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/426 ,  A61K45/06 ,  C07C211/01 ,  C07C211/29 ,  C07D231/38 ,  C07D277/38 ,  C07D277/42 ,  C07D277/46 ,  C07D277/60 ,  C07D405/14 ,  C07D409/04 ,  C07D413/12 ,  C07K14/47 ,  A61K2300/00

Abstract: The present invention relates to HSF activating compounds, methods for their discovery, and their research and therapeutic uses, as well as pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, mixtures (including both R and S enantiomeric forms and racemic mixtures thereof), and pharmaceutical Formulations thereof. In particular, the present invention provides compounds capable of facilitating HSF1 homotrimerization, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with irregular HSF1 activity.

Abstract translation: 本发明涉及HSF活化化合物，其发现方法及其研究和治疗用途，以及其药学上可接受的盐，溶剂合物，螯合物，非共价复合物，前药，混合物（包括R和S对映体形式和外消旋 其混合物）及其药物制剂。 特别地，本发明提供能够促进HSF1同源三聚化的化合物，以及使用这些化合物作为治疗剂来治疗与不规则HSF1活性相关的许多病症的方法。

公开(公告)号：US20160175351A1

公开(公告)日：2016-06-23

申请号：US14392336

申请日：2014-06-24

Applicant: DUKE UNIVERSITY

Inventor： Dennis J. Thiele ,  Helena Öhrvik

IPC: A61K33/24 ,  A61K45/06 ,  C12Q1/68

CPC classification number: A61K33/24 ,  A61K31/165 ,  A61K31/282 ,  A61K31/336 ,  A61K31/555 ,  A61K38/05 ,  A61K45/06 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N2800/52 ,  A61K2300/00

Abstract: Described herein are methods of inhibiting the proliferation of cancer cells and methods of treating cancer, as well as methods of predicting responsiveness of subjects to certain cancer treatments and methods of identifying subjects as candidates for certain cancer treatments.

Abstract translation: 本文描述了抑制癌细胞增殖的方法和治疗癌症的方法，以及预测受试者对某些癌症治疗的反应性的方法以及将受试者鉴定为某些癌症治疗的候选物的方法。

公开(公告)号：US20150017261A1

公开(公告)日：2015-01-15

申请号：US14371871

申请日：2013-01-11

Applicant: DUKE UNIVERSITY

Inventor： Chris M. Counter ,  Donita C. Brady ,  Michelle L. L. Turski ,  Dennis J. Thiele

IPC: A61K33/24 ,  A61K45/06

CPC classification number: A61K33/24 ,  A61K31/095 ,  A61K31/132 ,  A61K31/18 ,  A61K31/198 ,  A61K31/275 ,  A61K31/416 ,  A61K31/4523 ,  A61K31/4745 ,  A61K31/519 ,  A61K33/30 ,  A61K45/06 ,  A61K2300/00

Abstract: The present disclosure provides methods of treating and/or preventing cancer in a subject comprising administering to the subject a copper-reduced diet by itself or as a supplement along with a regular diet to create a copper-reduced melieu, maintain a reduced-copper melieu, or both, thereby treating and/or preventing the development of the cancer. Methods also comprise further adding a copper chelator, MEK inhibitor, or combinations thereof.

Abstract translation: 本公开提供了治疗和/或预防受试者癌症的方法，其包括向受试者施用减少铜的饮食本身或作为补充剂与常规饮食一起以产生铜还原甜菜，维持减少铜的甜味剂 ，或两者，从而治疗和/或预防癌症的发展。 方法还包括进一步加入铜螯合剂，MEK抑制剂或其组合。