公开(公告)号：US11008367B2

公开(公告)日：2021-05-18

申请号：US16233386

申请日：2018-12-27

Applicant: UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.

Inventor： Shin-je Ghim ,  A. Bennett Jenson ,  John O. Trent

IPC: C07K14/005 ,  A61K39/12 ,  C12N7/00 ,  A61K39/23 ,  C12N15/85 ,  C12P21/02 ,  A61K39/00

Abstract: Some embodiments of the invention include inventive polypeptides (e.g., mutant VP2 proteins) and virus-like particles made from the inventive polypeptides. Other embodiments of the invention include compositions for treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Further embodiments include methods for administering compositions to an animal. Other embodiments include treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Still other embodiments include nucleic acid sequences that encode the inventive polypeptides. Additional embodiments of the invention are also discussed.

公开(公告)号：US20170015712A1

公开(公告)日：2017-01-19

申请号：US15124699

申请日：2015-03-10

Applicant: University of Louisville Research Foundation, Inc.

Inventor： Shin-je Ghim ,  A. Bennett Jenson ,  John O. Trent

IPC: C07K14/005 ,  C12N15/85 ,  C12P21/02 ,  C12N7/00 ,  A61K39/23

CPC classification number: C07K14/005 ,  A61K39/12 ,  A61K39/23 ,  A61K2039/5258 ,  A61K2039/55511 ,  A61K2039/55566 ,  A61K2039/575 ,  C12N7/00 ,  C12N15/85 ,  C12N2710/14043 ,  C12N2750/14222 ,  C12N2750/14223 ,  C12N2750/14234 ,  C12P21/02 ,  Y02A50/412

Abstract: Some embodiments of the invention include inventive polypeptides (e.g., mutant VP2 proteins) and virus-like particles made from the inventive polypeptides. Other embodiments of the invention include compositions for treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Further embodiments include methods for administering compositions to an animal. Other embodiments include treating (e.g., preventing) par vovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Still other embodiments include nucleic acid sequences that encode the inventive polypeptides. Additional embodiments of the invention are also discussed.

Abstract translation: 本发明的一些实施方案包括本发明多肽（例如，突变VP2蛋白）和由本发明多肽制备的病毒样颗粒。 本发明的其它实施方案包括用于治疗（例如，预防）细小病毒（例如，红血病病毒或细小病毒B19）感染和其它疾病的组合物。 其它实施方案包括将组合物施用于动物的方法。 其他实施方案包括治疗（例如，预防）杆状病毒（例如红血病病毒或细小病毒B19）感染和其它疾病。 其它实施方案包括编码本发明多肽的核酸序列。 还讨论了本发明的另外的实施例。

公开(公告)号：US20150190379A1

公开(公告)日：2015-07-09

申请号：US14589050

申请日：2015-01-05

Applicant: The University of Louisville Research Foundation Inc.

Inventor： Chi Li ,  John O. Trent

IPC: A61K31/437 ,  A61K31/495 ,  A61K31/282

CPC classification number: A61K31/437 ,  A61K31/282 ,  A61K31/495 ,  A61K31/496 ,  A61K31/53

Abstract: The pro-apoptotic Bcl-2 protein Bax initiates apoptosis in almost all apoptotic paradigms. Agents facilitating disruptive Bax insertion into mitochondrial membranes have potential as cancer therapeutics. Small molecule compounds associating with the hydrophobic groove of the pro-apoptotic Bcl-2 protein Bax have been identified and found to promote Bax-dependent, but not Bak-dependent, apoptosis. The compounds alter Bax protein stability in vitro and promote Bax insertion into mitochondria, leading to Bax-dependent mitochondrial outer membrane permeabilization and apoptosis. The compounds activating the pro-apoptotic Bcl-2 protein Bax inhibit the growth of tumors by inducing apoptosis. Pharmaceutical compositions comprising the compounds that activate Bax and induce Bax-dependent apoptosis are useful as anti-cancer therapeutic agents alone or with other anti-cancer agents. Methods for inducing apoptosis and for treating cancer involve administering the compounds to a patient in need thereof.

Abstract translation: 促细胞凋亡的Bcl-2蛋白Bax在几乎所有的凋亡模式中启动细胞凋亡。 将破坏性Bax插入线粒体膜的药物具有作为癌症治疗剂的潜力。 已经鉴定了与促凋亡Bcl-2蛋白Bax的疏水沟相关的小分子化合物，以促进Bax依赖性，但不促进Bak依赖性凋亡。 该化合物在体外改变Bax蛋白稳定性，促进Bax插入线粒体，导致Bax依赖性线粒体外膜透化和凋亡。 激活促凋亡Bcl-2蛋白Bax的化合物通过诱导凋亡来抑制肿瘤的生长。 包含活化Bax并诱导Bax依赖性细胞凋亡的化合物的药物组合物可用作单独的抗癌治疗剂或与其它抗癌剂一起使用。 用于诱导细胞凋亡和治疗癌症的方法包括将化合物给予有需要的患者。

公开(公告)号：US11312690B2

公开(公告)日：2022-04-26

申请号：US15746819

申请日：2016-07-22

Applicant: UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.

Inventor： Geoffrey J. Clark ,  John O. Trent ,  Joseph A. Burlison ,  Nagaraju Miriyala

IPC: C07D239/95 ,  A61P35/04

Abstract: Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.

公开(公告)号：US10774046B2

公开(公告)日：2020-09-15

申请号：US16170391

申请日：2018-10-25

Applicant: UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.

Inventor： Sucheta Telang ,  Jason Chesney ,  John O. Trent ,  Joseph A. Burlison ,  Nagaraju Miriyala

IPC: C07D215/46 ,  C07D215/42 ,  A61P35/00 ,  A61K45/06 ,  A61K31/4706

Abstract: Some embodiments of the invention include inventive compounds. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Other embodiments include PFKFB4 inhibitors and methods of using the same that can target neoplastic cells, including, such as, mechanisms within those cells that relate to the use of the glycolytic pathway. In other embodiments, small molecule PFKFB4 inhibitors are used to disrupt the kinase domain of PFKFB4 and, in some instances, decrease the glucose metabolism and growth of human cancers. Additional embodiments of the invention are also discussed herein.

公开(公告)号：US20190202867A1

公开(公告)日：2019-07-04

申请号：US16233386

申请日：2018-12-27

Applicant: UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.

Inventor： Shin-je Ghim ,  A. Bennett Jenson ,  John O. Trent

IPC: C07K14/005 ,  A61K39/23 ,  A61K39/12 ,  C12N15/85 ,  C12N7/00 ,  C12P21/02

CPC classification number: C07K14/005 ,  A61K39/12 ,  A61K39/23 ,  A61K2039/5258 ,  A61K2039/55511 ,  A61K2039/55566 ,  A61K2039/575 ,  C12N7/00 ,  C12N15/85 ,  C12N2710/14043 ,  C12N2750/14222 ,  C12N2750/14223 ,  C12N2750/14234 ,  C12P21/02 ,  Y02A50/412

Abstract: Some embodiments of the invention include inventive polypeptides (e.g., mutant VP2 proteins) and virus-like particles made from the inventive polypeptides. Other embodiments of the invention include compositions for treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Further embodiments include methods for administering compositions to an animal. Other embodiments include treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Still other embodiments include nucleic acid sequences that encode the inventive polypeptides. Additional embodiments of the invention are also discussed.

公开(公告)号：US20140303170A1

公开(公告)日：2014-10-09

申请号：US14289712

申请日：2014-05-29

Applicant: University of Louisville Research Foundation, Inc.

Inventor： John O. Trent ,  Jason B. Meier ,  Kelby B. Napier

IPC: C07D403/12 ,  C07D217/24

CPC classification number: C07D403/12 ,  A61K31/132 ,  A61K31/335 ,  A61K31/4015 ,  A61K31/4045 ,  A61K31/41 ,  A61K31/4184 ,  A61K31/4188 ,  A61K31/4196 ,  A61K31/454 ,  A61K31/47 ,  A61K31/472 ,  A61K31/473 ,  A61K31/4965 ,  A61K31/498 ,  A61K31/4985 ,  C07D217/24

Abstract: Some embodiments of this invention include methods for treating disease and methods for administering a compound of Formula (I). In some aspects of the invention, diseases can be treated by administration of compositions comprising a compound of Formula (I). Pharmaceutical compositions of some embodiments of the present invention comprise a compound of Formula (I).

Abstract translation: 本发明的一些实施方案包括治疗疾病的方法和给予式（I）化合物的方法。 在本发明的一些方面，可以通过给予包含式（I）化合物的组合物来治疗疾病。 本发明一些实施方案的药物组合物包含式（I）的化合物。

公开(公告)号：US10881654B2

公开(公告)日：2021-01-05

申请号：US15568751

申请日：2016-04-22

Applicant: UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.

Inventor： Sucheta Telang ,  Jason Chesney ,  John O. Trent

IPC: A61K31/4706 ,  A61K31/47 ,  A61K31/4545 ,  A61P35/00

Abstract: Methods and pharmaceutical compositions for inhibiting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) and the treatment of cancer are described.

公开(公告)号：US10214565B2

公开(公告)日：2019-02-26

申请号：US15124699

申请日：2015-03-10

Applicant: University of Louisville Research Foundation, Inc.

Inventor： Shin-je Ghim ,  A. Bennett Jenson ,  John O. Trent

IPC: C07K14/005 ,  A61K39/12 ,  A61K39/23 ,  C12N7/00 ,  C12N15/85 ,  C12P21/02 ,  A61K39/00

Abstract: Some embodiments of the invention include inventive polypeptides (e.g., mutant VP2 proteins) and virus-like particles made from the inventive polypeptides. Other embodiments of the invention include compositions for treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Further embodiments include methods for administering compositions to an animal. Other embodiments include treating (e.g., preventing) parvovirus (e.g., erythrovirus or parvovirus B19) infection and other diseases. Still other embodiments include nucleic acid sequences that encode the inventive polypeptides. Additional embodiments of the invention are also discussed.

公开(公告)号：US20180009764A1

公开(公告)日：2018-01-11

申请号：US15708827

申请日：2017-09-19

Applicant: UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC. ,  ADVANCED CANCER THERAPEUTICS, LLC

Inventor： Robert A. Mitchell ,  John O. Trent ,  Pooran Chand ,  Gilles Hugues Tapolsky

IPC: C07D239/30 ,  C07D401/04 ,  C07D239/38 ,  C07D239/42 ,  C07D409/04 ,  C07D405/04

CPC classification number: C07D239/30 ,  C07D239/38 ,  C07D239/42 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04

Abstract: Compounds useful for the inhibition of macrophage migration inhibitory factor (MIF) are provided herein, having the Formula I: wherein A is selected from the group consisting of aromatic or non-aromatic rings, bicyclic rings, polycyclic rings, alkenes or alkynes; B is H, OH, OR, SR, NH2, NHR, or alkyl; R is H or alkyl, and X and Y are independently N or CH, but one of X and Y must be N. Also provided are pharmaceutical compositions that contain a Formula I compound and methods for the treatment of MIF-implicated diseases or conditions that include administering a safe and effective amount of a Formula I compound.