公开(公告)号：US11833147B2

公开(公告)日：2023-12-05

申请号：US17144926

申请日：2021-01-08

申请人： The Board of Trustees of the University of Illinois ,  Vanquish Oncology, Inc.

发明人： Paul J. Hergenrother ,  Rachel C. Botham ,  Timothy M. Fan ,  Mark J. Gilbert ,  Michael K. Handley ,  Howard S. Roth ,  Theodore M. Tarasow

IPC分类号： A61K31/495 ,  A61K33/243 ,  A61K9/08 ,  A61K31/138 ,  A61K31/282 ,  A61K31/337 ,  A61K31/496 ,  A61K31/553 ,  A61K31/704 ,  A61K31/7048 ,  A61K33/24 ,  A61K38/05 ,  A61K45/06 ,  A61K47/10 ,  A61K9/00 ,  A61K9/20 ,  A61K9/48

CPC分类号： A61K31/495 ,  A61K9/008 ,  A61K9/0019 ,  A61K9/08 ,  A61K9/2027 ,  A61K9/2054 ,  A61K9/2059 ,  A61K9/4858 ,  A61K31/138 ,  A61K31/282 ,  A61K31/337 ,  A61K31/496 ,  A61K31/553 ,  A61K31/704 ,  A61K31/7048 ,  A61K33/24 ,  A61K33/243 ,  A61K38/05 ,  A61K45/06 ,  A61K47/10 ,  A61K31/496 ,  A61K2300/00

摘要： The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.

公开(公告)号：US20220112203A1

公开(公告)日：2022-04-14

申请号：US17306008

申请日：2021-05-03

申请人： The Board of Trustees of the University of Illinois

发明人： Paul J. Hergenrother ,  Michelle Richter ,  Andrew Riley ,  Bryon S. Drown ,  Martin Chavez ,  Sarah Tasker ,  Alfredo Garcia

IPC分类号： C07D491/052 ,  C07D413/14 ,  C07D407/06 ,  C07D407/12 ,  C07D413/04 ,  C07D413/10 ,  C07C225/20 ,  C07D471/04 ,  C07D471/14 ,  C07D471/20 ,  C07D263/20 ,  C07D498/04 ,  C07J1/00 ,  C07J13/00 ,  C07J21/00 ,  C07J41/00 ,  C07J43/00 ,  C07J73/00 ,  A61P31/04 ,  C07D413/12 ,  C07D417/12

摘要： Disclosed are novel compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

公开(公告)号：US11274106B2

公开(公告)日：2022-03-15

申请号：US16624335

申请日：2018-06-21

申请人： THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

发明人： Paul J. Hergenrother ,  Andrew P. Riley

IPC分类号： C07D498/16

摘要： Herein is described the conversion of deoxynybomycin (DNM), a natural product and DNA gyrase inhibitor with minimal cytotoxicity, into a compound (Formula I) that has anticancer activity. Detailed in vitro and cell culture experiments demonstrate that these compounds inhibit Top2 and also act upon topoisomerase I. Similar approaches are applicable to other classes of gyrase inhibitors and other antibacterial targets for discovery of new anticancer drugs.

公开(公告)号：US10285986B2

公开(公告)日：2019-05-14

申请号：US15933671

申请日：2018-03-23

申请人： The Board of Trustees of the University of Illinois ,  The Board of Regents of the University of Texas System

发明人： Paul J. Hergenrother ,  David A. Boothman ,  Joseph S. Bair ,  Rahul Palchaudhuri ,  Elizabeth I. Parkinson

IPC分类号： A61K31/4745 ,  A61K31/47 ,  C07D471/04 ,  C07H15/26 ,  C07F9/6561 ,  A61K45/06

摘要： Compositions comprising Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compositions are useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.

公开(公告)号：US10272099B2

公开(公告)日：2019-04-30

申请号：US14783344

申请日：2014-04-08

申请人： The Board of Regents of the University of Texas System ,  The Board of Trustees of the University of Illinois

发明人： Paul J. Hergenrother ,  David A. Boothman ,  Joseph S. Bair ,  Lifen Cao ,  Jinming Gao ,  Xiumei Huang ,  Xiuquan Luo ,  Xinpeng Ma ,  Zachary R. Moore ,  Elizabeth I. Parkinson

IPC分类号： A61K31/353 ,  A61K31/4745 ,  A61K31/131 ,  A61K31/706 ,  A61K45/06 ,  C12Q1/6886 ,  A61K31/4738

摘要： The therapies described herein can be selectively lethal toward a variety of different cancer cell types and cancer conditions in a subject. The combination therapies described herein can be useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy, particularly where the disease is accompanied by elevated levels of NQO1.

公开(公告)号：US10081592B2

公开(公告)日：2018-09-25

申请号：US14387028

申请日：2013-03-25

申请人： THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS ,  Paul J. Hergenrother ,  Robert W. Huigens, III ,  Karen C. Morrison ,  Robert W. Hicklin, II ,  Timothy A. Flood, Jr.

发明人： Paul J. Hergenrother ,  Robert W. Huigens, III ,  Karen C. Morrison ,  Robert W. Hicklin, II ,  Timothy A. Flood, Jr.

IPC分类号： C07D401/14 ,  C07C69/757 ,  C07D311/94 ,  C07D313/06 ,  C07D223/14 ,  C07D401/04 ,  C07D471/04 ,  C07D471/08 ,  C07D493/08 ,  C07D513/04 ,  C07D519/00 ,  C07D303/10 ,  C07C59/205 ,  C07C62/32 ,  C07C62/38 ,  C07B37/06 ,  C07B37/08 ,  C07D307/93 ,  C07D313/08 ,  C07D405/06 ,  C07D405/12 ,  C07D413/06 ,  C07J21/00 ,  C07J69/00 ,  C07J71/00 ,  C07J73/00 ,  C07J75/00

CPC分类号： C07C69/757 ,  C07B37/06 ,  C07B37/08 ,  C07C59/205 ,  C07C62/32 ,  C07C62/38 ,  C07C2601/16 ,  C07C2602/44 ,  C07C2603/86 ,  C07D223/14 ,  C07D303/10 ,  C07D307/93 ,  C07D311/94 ,  C07D313/06 ,  C07D313/08 ,  C07D401/04 ,  C07D401/14 ,  C07D405/06 ,  C07D405/12 ,  C07D413/06 ,  C07D471/04 ,  C07D471/08 ,  C07D493/08 ,  C07D513/04 ,  C07D519/00 ,  C07J21/008 ,  C07J69/00 ,  C07J71/001 ,  C07J71/0031 ,  C07J73/005 ,  C07J73/008 ,  C07J75/005

摘要： The invention a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.

公开(公告)号：US09682060B2

公开(公告)日：2017-06-20

申请号：US15295921

申请日：2016-10-17

申请人： The Board of Trustees of the University of Illinois

发明人： Paul J. Hergenrother ,  Karson S. Putt ,  Rahul Palchaudhuri

IPC分类号： A61K31/343 ,  A61K31/11

CPC分类号： A61K31/343 ,  A61K31/11 ,  A61K45/06

摘要： Apoptosis is generally believed to be a process that requires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis. We describe herein the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes, in multiple different cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the critical roles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility to study apoptosis in vivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery.

公开(公告)号：US09434736B2

公开(公告)日：2016-09-06

申请号：US14490146

申请日：2014-09-18

申请人： Massachusetts Institute of Technology ,  The Board of Trustees of the University of Illinois

发明人： Mohammad Movassaghi ,  Paul J. Hergenrother

IPC分类号： A61K31/498 ,  C07D487/14

CPC分类号： A61K31/4985 ,  A61K31/498 ,  C07D487/14

摘要： The present invention, among other things, provides compounds, compositions and methods for treatment of cancer. In some embodiments, the present invention provides methods for treating blood cancer using agelastatin alkaloids.

摘要翻译： 本发明尤其提供了用于治疗癌症的化合物，组合物和方法。 在一些实施方案中，本发明提供了使用阿霉素生物碱治疗血液癌的方法。

公开(公告)号：US20160122348A1

公开(公告)日：2016-05-05

申请号：US14993029

申请日：2016-01-11

申请人： The Board of Trustees of the University of Illinois ,  The Board of Regents of the University of Texas System

发明人： Paul J. Hergenrother ,  David A. Boothman ,  Joseph S. Bair ,  Rahul Palchaudhuri ,  Elizabeth I. Parkinson

IPC分类号： C07D471/04

CPC分类号： A61K31/4745 ,  A61K31/47 ,  A61K45/06 ,  C07D471/04 ,  C07F9/6561 ,  C07H15/26

摘要： Compounds of Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compounds are useful for the management, treatment, control or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.

摘要翻译： 对于各种不同的癌细胞类型，式（I）的化合物可以选择性致死。 这些化合物可用于治疗，治疗，控制或辅助治疗疾病，其中选择性致死性在化学治疗中是有益的。

公开(公告)号：US20150025083A1

公开(公告)日：2015-01-22

申请号：US14383460

申请日：2013-03-06

申请人： THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS ,  VANQUISH ONCOLOGY, INC.

发明人： Paul J. Hergenrother ,  Rachel C. Botham ,  Timothy M. Fan ,  Mark J. Gilbert ,  Michael J. Handley ,  Avadhut Joshi ,  Gregory J. Riggins ,  Theodore M. Tarasow

IPC分类号： A61K31/495

CPC分类号： A61K31/495 ,  A61K9/0019 ,  A61K9/008 ,  A61K9/2018 ,  A61K9/2054 ,  A61K9/4858 ,  A61K31/4188 ,  A61K47/10 ,  A61K2300/00

摘要： The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.

摘要翻译： 本发明提供了诱导细胞死亡的组合物和方法，例如癌细胞死亡。 公开了化合物和相关使用方法的组合，包括在治疗中使用化合物治疗癌症和选择性诱导细胞凋亡。 所公开的药物组合可以具有比其它化合物和化合物组合更低的神经毒性作用。