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1. 发明申请

WO2020146657A1 PI4-KINASE INHIBITORS WITH ANTI-CANCER ACTIVITY 审中-公开
公开(公告)号：WO2020146657A1
公开(公告)日：2020-07-16
申请号：PCT/US2020/012965
申请日：2020-01-09
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , GLENN, Jeffrey S. , SMITH, Mark , PHAM, Edward
发明人： GLENN, Jeffrey S. , SMITH, Mark , PHAM, Edward
IPC分类号： C07D277/40 , C07D277/42 , C07D277/46
摘要： Methods of treating a subject for cancer using a PI4-kinase inhibitor are provided. Also provided are methods of inhibiting PI4-kinase in a cancer cell to reduce cellular proliferation. The PI4-kinase inhibitor can be a compound that is a 5-aryl or heteroaryl-thiazole, e.g., as described herein. In certain embodiments, the PI4-kinase inhibitor is a substituted 2-amino-5-phenylthiazole or substituted 2-amino-5-pyridylthiazole compound. The subject compounds may be formulated or provided to a subject in combination with one or more additional anti-cancer agents. Use of PI4-kinase inhibitors in methods of reducing cellular proliferation and methods of treatment is provided in a variety of cancer cells and cancer subjects.

2. 发明申请

WO2020191205A1 PI4-KINASE INHIBITORS AND METHODS OF USING THE SAME 审中-公开
公开(公告)号：WO2020191205A1
公开(公告)日：2020-09-24
申请号：PCT/US2020/023654
申请日：2020-03-19
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , GLENN, Jeffrey S. , SMITH, Mark , PHAM, Edward A. , BASU, Kaustabh , STABLER, Stephen
发明人： GLENN, Jeffrey S. , SMITH, Mark , PHAM, Edward A. , BASU, Kaustabh , STABLER, Stephen
IPC分类号： C07D277/42 , A61K31/426 , A61K45/06 , A61P35/00
摘要： Compounds and methods are provided for inhibiting a PI4-kinase. Methods of treating a pathogen infection and methods of treating cancer are also provided. The PI4-kinase inhibitor can be a compound that is a 5-aryl or heteroaryl-thiazole, e.g., as described herein. In certain embodiments, the PI4-kinase inhibitor is a substituted 2-amino-5-phenylthiazole or substituted 2-amino-5-pyridylthiazole compound. In some embodiments, the compounds have broad spectrum anti-infective activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of treating a subject for cancer using a PI4-kinase inhibitor. Aspects of the methods include inhibiting PI4-kinase in a cancer cell to reduce cellular proliferation.

3. 发明申请

WO2005032329A2 METHODS AND COMPOSITIONS FOR IDENTIFYING ANTI-HCV AGENTS 审中-公开
标题翻译：鉴定抗HCV药物的方法和组合物
公开(公告)号：WO2005032329A2
公开(公告)日：2005-04-14
申请号：PCT/US2004/027070
申请日：2004-08-18
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , GLENN, Jeffrey S. , EINAV, Shirit , ELAZAR, Menashe
发明人： GLENN, Jeffrey S. , EINAV, Shirit , ELAZAR, Menashe
IPC分类号： A61B
CPC分类号： G01N33/5767 , C12Q1/707 , G01N33/56983 , G01N33/6875 , G01N2333/18 , G01N2500/04
摘要： The invention provides methods and compositions for identifying agents for treating infection by viruses that encode a nucleotide-binding NS4B protein, or functional equivalent thereof, e.g., hepatitis C virus (HCV) or other members of the family Flaviviridae. In general, the methods involve contacting an NS4B nucleotide binding motif (NBM)-containing polypeptide with a candidate agent, and determining the effect of the candidate agent on nucleotide binding activity, a nucleotide hydrolyzing activity, or a nucleotide-dependent RNA binding activity of the polypeptide. A candidate agent that inhibits NS4B polypeptide binding to a nucleotide is an anti-viral agent, e.g., an anti-HCV agent. The invention also features a polynucleotide encoding a NS4B polypeptide having a modified NBM (e.g., which is impaired in NTP binding). The subject methods and compositions find use in a variety of therapeutic and screening applications.
摘要翻译：本发明提供用于鉴定用于治疗编码与核苷酸结合的NS4B蛋白或其功能等同物如丙型肝炎病毒（HCV）或黄病毒科的其他成员的病毒感染的药剂的方法和组合物。通常，所述方法包括将含NS4B核苷酸结合基序（NBM）的多肽与候选试剂接触，并确定候选试剂对核苷酸结合活性，核苷酸水解活性或核苷酸依赖性RNA结合活性的影响多肽。抑制NS4B多肽与核苷酸结合的候选试剂是抗病毒剂，例如抗HCV剂。本发明还特征在于编码具有修饰的NBM（例如其在NTP结合中受损的）的NS4B多肽的多核苷酸。主题方法和组合物可用于各种治疗和筛选应用。

4. 发明申请

WO2012054809A2 RAPID HIGH RESOLUTION, HIGH THROUGHPUT RNA STRUCTURE, RNA-MACROMOLECULAR INTERACTION, AND RNA-SMALL MOLECULE INTERACTION MAPPING 审中-公开
标题翻译：快速高分辨率，高通量RNA结构，RNA-大分子相互作用和RNA-小分子相互作用图
公开(公告)号：WO2012054809A2
公开(公告)日：2012-04-26
申请号：PCT/US2011/057232
申请日：2011-10-21
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , GLENN, Jeffrey S. , PANG, Phillip S. , PATEL, Shripa
发明人： GLENN, Jeffrey S. , PANG, Phillip S. , PATEL, Shripa
IPC分类号： C12Q1/68
CPC分类号： C12Q1/707 , C12Q1/68 , G06F19/22 , C12Q2521/107 , C12Q2525/155 , C12Q2525/204 , C12Q2565/133
摘要： Compositions and methods are provided for a rapid, high-resolution, high-throughput method for determining the intramolecular interactions between the nucleotides present in an polynucleotide, such that single-stranded nucleotides, and nucleotides in a double-stranded configuration are distinguished and identified. Tertiary contacts and solvent accessible regions may also be determined, where such contacts and regions may result from a single stranded configuration, intermolecular interactions with other macromolecules including, without limitation, DNA, protein, RNA, etc.; intermolecular interactions with small molecules which may include drug candidates; or a combination of macromolecules and small molecules.
摘要翻译：提供组合物和方法用于确定存在于多核苷酸中的核苷酸之间的分子内相互作用的快速，高分辨率，高通量的方法，从而区分和鉴定双链构型中的单链核苷酸和核苷酸。也可以确定三级接触和溶剂可及区域，其中这种接触和区域可以由单链构型产生，与其它大分子的分子间相互作用，包括但不限于DNA，蛋白质，RNA等; 与可能包括药物候选物的小分子的分子间相互作用; 或大分子和小分子的组合。

5. 发明申请

WO2010039195A2 SCREENING FOR INHIBITORS OF HCV AMPHIPATHIC HELIX (AH) FUNCTION 审中-公开
标题翻译：筛选HCV雄性HELIX（AH）功能的抑制剂
公开(公告)号：WO2010039195A2
公开(公告)日：2010-04-08
申请号：PCT/US2009/005306
申请日：2009-09-23
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , GLENN, Jeffrey S. , CHO, Nam-Joon , YANG, Wenjin
发明人： GLENN, Jeffrey S. , CHO, Nam-Joon , YANG, Wenjin
IPC分类号： C12Q1/70
CPC分类号： C07K14/005 , C12N2770/24222
摘要： Screening methods are provided for identifying pharmacologic inhibitors of HCV amphipathic helix (AH) function, which inhibitors are useful in the prevention and treatment of HCV infection. Also provided are compounds useful in the inhibition of viral replication. The methods of the invention are based on the unexpected discovery that the presence of an AH, e.g. an AH of an HCV polypeptide, causes an increase in the apparent diameter of the vesicles. The methods of the invention provide for addition of AH peptides to lipid vesicles, for example in a high-throughput format; which addition may be performed in the absence or presence of a candidate pharmacologic agent. The change in apparent vesicle size is measured, and compared to control samples. An increase in vesicle size or aggregation is indicative of AH function being present; and a lack of increase is indicative that the AH function is absent or has been inhibited by a test agent.
摘要翻译：提供筛选方法用于鉴定HCV两亲性螺旋（AH）功能的药理学抑制剂，该抑制剂可用于预防和治疗HCV感染。还提供了可用于抑制病毒复制的化合物。本发明的方法基于意想不到的发现，即AH的存在，例如， HCV多肽的AH引起囊泡表观直径的增加。本发明的方法提供了将AH肽添加到脂质囊泡中，例如以高通量形式加入; 该添加可以在不存在或存在候选药理剂的情况下进行。测量明显囊泡大小的变化，并与对照样品进行比较。囊泡大小或聚集的增加表明存在AH功能; 并且缺乏增加表明AH功能不存在或已被测试者抑制。

6. 发明申请

WO2009005615A1 METHODS AND COMPOSITIONS FOR IDENTIFYING AGENTS THAT INHIBIT AN NS4B-MEDIATED NEOPLASTIC CELLULAR PHENOTYPE OF HCV INFECTED CELLS 审中-公开
标题翻译：用于鉴定抑制NS4B介导的HCV感染细胞的神经细胞细胞的方法和组合物
公开(公告)号：WO2009005615A1
公开(公告)日：2009-01-08
申请号：PCT/US2008/007760
申请日：2008-06-20
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , GLENN, Jeffrey S. , EINAV, Shirit
发明人： GLENN, Jeffrey S. , EINAV, Shirit
IPC分类号： C12Q1/68 , G01N33/567
CPC分类号： G01N33/5011 , A61K49/0008
摘要： The disclosure provides methods and compositions for identifying agents that inhibit a neoplastic cellular phenotype mediated by the NS4B protein nucleotide binding motif (NBM) of hepatitis C virus (HCV). In general, the methods involve contacting a candidate agent with a mammalian cell expressing an NS4B NBM polypeptide of an HCV virus, wherein expression of the NS4B NBM polypeptide in the absence of candidate agent promotes a neoplastic cellular phenotype, and detecting the presence or absence of an effect of said candidate agent on NS4B-mediated promotion of a neoplastic cellular phenotype. The disclosed methods and compositions find use in a variety of therapeutic and screening applications.
摘要翻译：本公开提供用于鉴定抑制由丙型肝炎病毒（HCV）的NS4B蛋白核苷酸结合基序（NBM）介导的肿瘤细胞表型的药剂的方法和组合物。通常，所述方法包括使候选试剂与表达HCV病毒的NS4B NBM多肽的哺乳动物细胞接触，其中NS4B NBM多肽在不存在候选试剂的情况下的表达促进肿瘤细胞表型，并检测是否存在所述候选试剂对NS4B介导的肿瘤细胞表型的促进的作用。所公开的方法和组合物可用于各种治疗和筛选应用。

7. 发明申请

WO2017151795A1 PAN-GENOTYPIC AGENTS AGAINST INFLUENZA VIRUS AND METHODS OF USING THE SAME 审中-公开
标题翻译：针对流感病毒的泛基因型药物及其使用方法
公开(公告)号：WO2017151795A1
公开(公告)日：2017-09-08
申请号：PCT/US2017/020241
申请日：2017-03-01
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
发明人： GLENN, Jeffrey S. , HAGEY, Rachel , PHAM, Edward
IPC分类号： A61K48/00 , A61K31/7056 , A61K31/545 , A61K31/5377 , A61K31/43 , A61K31/165
摘要： Methods of inhibiting influenza A virus in a sample are provided. Aspects of the methods include contacting a sample comprising viral RNA (vRNA) having a PSL2 motif with an effective amount of an agent that specifically binds the PSL2 motif to inhibit the influenza A virus. Also provided are methods of treating or preventing influenza A virus infection in a subject. Also provided are methods for screening a candidate agent for the ability to inhibit influenza A virus in a cell, the method comprising: contacting a sample with a candidate agent; and determining whether the candidate agent specifically binds to the PSL2 motif of vRNA. Also provided are compounds and pharmaceutical compositions comprising an oligonucleotide sequence complementary to a PB2 vRNA region that find use in the subject methods.
摘要翻译：提供了抑制样品中甲型流感病毒的方法。方法的各方面包括使包含具有PSL2基序的病毒RNA（vRNA）的样品与有效量的特异性结合PSL2基序以抑制甲型流感病毒的药剂接触。还提供了治疗或预防受试者中的甲型流感病毒感染的方法。还提供了筛选候选药剂在细胞中抑制甲型流感病毒的能力的方法，所述方法包括：使样品与候选药剂接触; 并确定候选药剂是否特异性结合vRNA的PSL2基序。还提供了包含与用于本方法的PB2 vRNA区域互补的寡核苷酸序列的化合物和药物组合物。

8. 发明申请

WO2017147526A1 PI-KINASE INHIBITORS WITH ANTI-INFECTIVE ACTIVITY 审中-公开
标题翻译：具有抗感染活性的PI-激酶抑制剂
公开(公告)号：WO2017147526A1
公开(公告)日：2017-08-31
申请号：PCT/US2017/019509
申请日：2017-02-24
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
发明人： GLENN, Jeffrey S. , GELMAN, Michael A. , TAVSHANJIAN, Brandon , SHOKAT, Kevan , CHOONG, Ingrid , SMITH, Mark
IPC分类号： C07D498/04 , C07D419/04
CPC分类号： C07D277/46 , C07D277/42 , C07D417/04 , C07D417/12 , C07D417/14
摘要： Compounds and methods are provided for the treatment of pathogen infections. In some embodiments, the anti-infective compounds have broad spectrum activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of inhibiting a PI4-kinase and methods of inhibiting viral infection. In some embodiments, the compound is a PI4-kinase inhibiting compound that is a 5-aryl-thiazole or a 5-hetereoaryl-thiazole. The subject compounds may be formulated or provided to a subject in combination with a second anti-infective agent, e.g. interferon, ribivarin, and the like.
摘要翻译：提供了用于治疗病原体感染的化合物和方法。在一些实施方案中，抗感染化合物对各种感染性疾病具有广谱活性，其中所述疾病由含有与磷脂酰肌醇4,5-二磷酸相互作用的碱性氨基酸PIP-2钳（BAAPP）结构域的病原体引起 PIP-2）介导病原体复制。还提供了抑制PI4-激酶的方法和抑制病毒感染的方法。在一些实施方案中，所述化合物是为5-芳基 - 噻唑或5-杂芳基 - 噻唑的PI4-激酶抑制性化合物。可以将主题化合物与第二种抗感染剂例如联合给药组合或配制给受试者。干扰素，ribivarin等。

9. 发明申请

WO2021201996A1 PAN-GENOTYPIC AGENTS AGAINST RESPIRATORY VIRUSES AND METHODS OF USING THE SAME 审中-公开
公开(公告)号：WO2021201996A1
公开(公告)日：2021-10-07
申请号：PCT/US2021/018025
申请日：2021-02-12
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
发明人： GLENN, Jeffrey S. , HAGEY, Rachel , PHAM, Edward A.
IPC分类号： C12N15/11 , A61P31/16
摘要： Methods of inhibiting a respiratory virus, (i.e., a virus associated with a respiratory condition, e.g., influenza A, influenza B, RSV, etc.) in a sample are provided. Aspects of the methods include contacting a sample comprising viral RNA (vRNA) having a target motif with an effective amount of an agent that specifically binds the target motif to inhibit the respiratory virus. Also provided are methods of treating or preventing respiratory virus infection in a subject. Also provided are compounds and pharmaceutical compositions comprising an oligonucleotide sequence complementary to a target vRNA region that find use in the subject methods.

10. 发明申请

WO2021183735A1 PULMONARY AGENT DELIVERY METHODS AND COMPOSITIONS FOR PRACTICING THE SAME 审中-公开
公开(公告)号：WO2021183735A1
公开(公告)日：2021-09-16
申请号：PCT/US2021/021855
申请日：2021-03-11
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
发明人： GLENN, Jeffrey S. , ELAZAR, Menashe , PHAM, Edward A. , SALUTI, Rachel
IPC分类号： A61K9/16 , A61P11/02 , A61P11/12 , A01N25/34 , A61P11/06 , A61K9/50
摘要： Methods of delivering a pulmonary agent to a cell are provided. Aspects of embodiments of the methods include contacting a cell with a pulmonary agent delivery composition, where the composition includes a pulmonary agent and a deproteinized pollen shell component. In some instances, the pulmonary agent delivery composition further includes a transfection agent. Also provided are pulmonary agent delivery compositions, as well as delivery devices, systems and kits, e.g., that find use in practicing the methods. The methods and compositions find use in a variety of different applications, including the treatment or prevention of lung conditions.

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