公开(公告)号：US12234504B1

公开(公告)日：2025-02-25

申请号：US18903582

申请日：2024-10-01

Applicant: Fenfei Leng ,  Matthew Dias

Inventor： Fenfei Leng ,  Matthew Dias

IPC: C12Q1/682 ,  C12Q1/37 ,  C12Q1/44 ,  C12Q1/533 ,  C12Q1/6832

Abstract: The subject invention provides a novel fluorescence-based, T5 exonuclease-amplified DNA cleavage assay for gyrase poisoning inhibitor discovery. According to the assay, multiple gyrase molecules can simultaneously bind to a plasmid DNA molecule to form multiple gyrase-DNA cleavage complexes on the same plasmid. These gyrase-DNA cleavage complexes, greatly stabilized by a gyrase poisoning inhibitor, and can be trapped by a detergent such as sarkosyl. Digestion of gyrase by proteinase K results in the production of small DNA fragments, which can be digested by T5 exonuclease. This fluorescence-based DNA cleavage HTS assay is also suitable for screening large compound libraries to identify inhibitors against DNA topoisomerases, including human DNA topoisomerase IIα.

公开(公告)号：US11732286B2

公开(公告)日：2023-08-22

申请号：US17670738

申请日：2022-02-14

Applicant: Fenfei Leng ,  Zifang Deng

Inventor： Fenfei Leng ,  Zifang Deng

IPC: C12Q1/68 ,  C07H21/00 ,  C12Q1/533 ,  C12Q1/44 ,  G01N21/64

CPC classification number: C12Q1/533 ,  C12Q1/44 ,  G01N21/6428 ,  G01N2021/6439 ,  G01N2500/04 ,  G01N2500/20

Abstract: The present invention provides assays and methods for studying DNA topology and topoisomerases. The assays and methods utilize a circular plasmid DNA comprising one or more hairpin structures and the ability of T5 exonuclease (T5E) to digest the circular plasmid DNA in a specific configuration. The assays and methods can be used as a high throughput screening for inhibitors of, for example, DNA gyrases and DNA topoisomerases I for anticancer drug and antibiotics discovery.

公开(公告)号：US20220119858A1

公开(公告)日：2022-04-21

申请号：US17072502

申请日：2020-10-16

Applicant: Fenfei LENG ,  Zifang Deng

Inventor： Fenfei LENG ,  Zifang Deng

IPC: C12Q1/533 ,  C12Q1/44 ,  G01N21/64

Abstract: The present invention provides assays and methods for studying DNA topology and topoisomerases. The assays and methods utilize a circular plasmid DNA comprising one or more hairpin structures and the ability of T5 exonuclease (T5E) to digest the circular plasmid DNA in a specific configuration. The assays and methods can be used as a high throughput screening for inhibitors of, for example, DNA gyrases and DNA topoisomerases I for anticancer drug and antibiotics discovery.

公开(公告)号：US20210405060A1

公开(公告)日：2021-12-30

申请号：US17161505

申请日：2021-01-28

Applicant: Revolution Medicines, Inc.

Inventor： Gregory L. VERDINE ,  M. James NICHOLS ,  Sharon A. TOWNSON ,  Uddhav Kumar SHIGDEL ,  Seung-Joo LEE ,  Dylan T. STILES ,  Neville J. ANTHONY

IPC: G01N33/68 ,  C07K1/13 ,  C07K5/02 ,  C07K7/64 ,  C12Q1/533 ,  G01N33/566 ,  C07K5/062 ,  C07K1/08 ,  C07K5/083

Abstract: The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

公开(公告)号：US20210371855A1

公开(公告)日：2021-12-02

申请号：US17252430

申请日：2019-06-17

Applicant: IDEAYA BIOSCIENCES, INC.

Inventor： Lisa BELMONT ,  Jeff HAGER ,  Yujiro HATA ,  Lorn KATEGAYA

IPC: C12N15/11 ,  A61P35/00 ,  A61K31/4015 ,  A61K47/68 ,  C12N15/113 ,  C12N9/22 ,  A61K38/46 ,  A61K31/7088 ,  C12N15/86 ,  C12N9/10 ,  A61K38/45 ,  C12Q1/533 ,  A61K45/06

Abstract: The present invention provides methods of negatively modulating the Werner protein (WRN) to inhibit proliferative cells characterized by high microsatellite instability (MSI-H), for example to treat proliferative diseases (such as cancer) characterized by high MSI (MSI-H). Further provided are compositions used in such methods.

公开(公告)号：US10604807B2

公开(公告)日：2020-03-31

申请号：US15570710

申请日：2016-05-18

Applicant: Corcept Therapeutics, Inc.

Inventor： Joseph K. Belanoff ,  Hazel Hunt ,  John Francis Unitt ,  Andreas G. Moraitis

IPC: A61K31/567 ,  C12Q1/6883 ,  A61K31/573 ,  A61K45/06 ,  G01N33/573 ,  C12Q1/533 ,  A61P5/46 ,  A61K31/4745 ,  G01N33/74

Abstract: Methods are provided for assessing a clinical response to a glucocorticoid receptor antagonist (GRA) in a human subject and for diagnosing Cushing's syndrome.

公开(公告)号：US10466249B2

公开(公告)日：2019-11-05

申请号：US15974923

申请日：2018-05-09

Applicant: Warp Drive Bio, Inc.

Inventor： Gregory L. Verdine ,  M. James Nichols ,  Sharon A. Townson ,  Uddhav Kumar Shigdel ,  Seung-Joo Lee ,  Dylan T. Stiles ,  Neville J. Anthony

IPC: G01N33/68 ,  C07K1/08 ,  C07K5/083 ,  C07K7/64 ,  C07K1/13 ,  C07K5/02 ,  C12Q1/533 ,  G01N33/566 ,  C07K5/062

Abstract: The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

公开(公告)号：US20180296554A1

公开(公告)日：2018-10-18

申请号：US15949703

申请日：2018-04-10

Applicant: UNIVERSITY OF SOUTH FLORIDA

Inventor： JONATHAN JACOB SABBAGH ,  CHAD DICKEY

IPC: A61K31/496 ,  A61K45/06 ,  A61K31/454 ,  A61K31/46 ,  A61K31/42 ,  A61K31/15 ,  A61K31/137 ,  A61K31/4168 ,  A61K31/5415 ,  C12Q1/533 ,  A61K31/36 ,  A61K31/138 ,  A61K31/135

CPC classification number: A61K31/496 ,  A61K31/135 ,  A61K31/137 ,  A61K31/138 ,  A61K31/15 ,  A61K31/36 ,  A61K31/4168 ,  A61K31/42 ,  A61K31/454 ,  A61K31/46 ,  A61K31/5415 ,  A61K45/06 ,  C12Q1/533 ,  G01N2333/99 ,  A61K2300/00

Abstract: The subject invention concerns materials and methods for treating depression, stress disorders, such as PTSD, anxiety disorders, and/or a neurodegenerative disease or condition in a person or animal. In one embodiment, a person or animal in need of treatment is administered one or more compounds or drugs, or a composition comprising the one or more compounds or drugs, that inhibit FKBP51 activity or function. The subject invention also concerns a method for inhibiting activity of the FKBP51 protein in a cell. The subject invention also concerns methods of screening for compounds or drugs that inhibit the FKBP51 protein.

公开(公告)号：US20170137895A1

公开(公告)日：2017-05-18

申请号：US15311006

申请日：2015-05-15

Applicant: ZYMONOSTICS APS

Inventor： Magnus Stougaard ,  Birgitta Ruth Knudsen ,  Marianne Smedegaard Hede ,  Jonas Thomsen ,  Yi-Ping Ho

IPC: C12Q1/68 ,  C12Q1/48 ,  C12Q1/533

CPC classification number: C12Q1/6893 ,  C12Q1/025 ,  C12Q1/04 ,  C12Q1/25 ,  C12Q1/485 ,  C12Q1/533 ,  C12Q1/68 ,  C12Q1/689 ,  G01N33/573 ,  G01N2333/9015 ,  G01N2333/91245 ,  G01N2800/26 ,  Y02A50/58 ,  C12Q2521/501 ,  C12Q2533/107 ,  C12Q2565/629 ,  C12Q2521/507 ,  C12Q2521/519

Abstract: The invention provides a method of identifying a microorganism that expresses a nucleic acid-modifying enzyme, in sample, the method comprising: (a) contacting a nucleic acid substrate targeted by the nucleic acid-modifying enzyme with the sample; (b) adding a further nucleic acid molecule to the sample which nucleic acid molecule is ligated to the nucleic acid substrate in the presence of the nucleic acid-modifying enzyme to form a ligation product which comprises a linear single strand of nucleic acid that is capable of being detected; and (c) detecting the presence of the ligation product.

公开(公告)号：US09487818B2

公开(公告)日：2016-11-08

申请号：US13825750

申请日：2011-09-22

Applicant: Somasundaram Kumaravel ,  Arivazhagan Arimappamagan ,  Kandavel Thennarasu ,  Alangar Sathyaranjandas Hegde ,  Ashwathnarayana Chandramouli ,  Santosh Vani ,  Paturu Kondaiah ,  Satyanarayana Rao Manchanahalli Rangaswamy

Inventor： Somasundaram Kumaravel ,  Arivazhagan Arimappamagan ,  Kandavel Thennarasu ,  Alangar Sathyaranjandas Hegde ,  Ashwathnarayana Chandramouli ,  Santosh Vani ,  Paturu Kondaiah ,  Satyanarayana Rao Manchanahalli Rangaswamy

IPC: C12Q1/533 ,  A61K31/495 ,  G01N33/574

CPC classification number: C12Q1/533 ,  A61K31/495 ,  C12Q2600/158 ,  C12Q2600/178 ,  G01N33/57407 ,  G01N2333/99 ,  G01N2800/52

Abstract: The present invention provides a TOP2A inhibition by temozolomide useful for predicting glioblastoma patient's survival. Glioblastoma (GBM) is the most common, malignant primary adult brain tumor. The conventional treatments for GBM, include surgery, radiation, and chemotherapy which have only modestly improved patient survival. The patients with GBM expressing higher TOP2A transcript levels had better prognosis. More interestingly, the present invention reports that temozolomide is an inhibitor of TOP2A activity in vitro. The present invention further shows that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. Thus it is demonstrated for the first time that temozolomide is a TOP2A inhibitor and establishes that TOP2A transcript levels determines the chemosensitivity of glioblastoma to temozolomide therapy thus explaining the very high levels of TOP2A transcript being a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.

Abstract translation: 本发明提供了可用于预测胶质母细胞瘤患者生存的替莫唑胺的TOP2A抑制。 成胶质细胞瘤（GBM）是最常见的恶性原发性成人脑肿瘤。 GBM的常规治疗方法包括手术，放射和化疗，只能适度改善患者的生存。 具有较高TOP2A转录水平的GBM患者预后较好。 更有趣的是，本发明报道了替莫唑胺是体外TOP2A活性的抑制剂。 本发明进一步显示，TOP2A的siRNA敲低使得对替莫唑胺化疗有抗性的胶质瘤细胞系。 因此，第一次证明替莫唑胺是TOP2A抑制剂，并且确定TOP2A转录物水平决定了胶质母细胞瘤对替莫唑胺治疗的化学敏感性，从而解释了非常高水平的TOP2A转录物是接受替莫唑胺化疗的GBM患者中良好的预后指标。