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1. 发明申请

WO2009016385A1 METHODS OF AIDING IN THE DIAGNOSIS OF PROSTATE CANCER 审中-公开
标题翻译：在前列腺癌诊断中的辅助方法
公开(公告)号：WO2009016385A1
公开(公告)日：2009-02-05
申请号：PCT/GB2008/002618
申请日：2008-07-31
申请人： IMPERIAL INNOVATIONS LIMITED , ALI, Simak , BULUWELA, Laki , WAXMAN, Jonathan , NGAN, Sarah
发明人： ALI, Simak , BULUWELA, Laki , WAXMAN, Jonathan , NGAN, Sarah
IPC分类号： G01N33/574 , C12Q1/68
CPC分类号： G01N33/57434 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158 , G01N2333/58
摘要： A method for aiding in the assessment of prostate cancer (including metastatic prostate cancer) and/or benign prostate hyperplasia in a patient, the method comprising the step of determining the level of CNP nucleic acid and/or protein in a sample from the patient. The patient may be at risk of developing prostate cancer, or have already been diagnosed with prostate cancer, or may have undergone treatment for prostate cancer. The method may be for assessing the likely progression of prostate cancer in the patient, or for assessing prostate function, or for assessing and/or predicting the development of prostate cancer. The method may be for diagnosing prostate cancer in the patient or for assessing the response of the patient to treatment for prostate cancer.
摘要翻译：一种用于帮助评估患者中前列腺癌（包括转移性前列腺癌）和/或良性前列腺增生的方法，所述方法包括测定患者样品中CNP核酸和/或蛋白质水平的步骤。患者可能处于发展中的前列腺癌的危险之中，或者已被诊断患有前列腺癌，或可能已经接受前列腺癌治疗。该方法可以用于评估患者中前列腺癌的可能进展，或用于评估前列腺功能，或用于评估和/或预测前列腺癌的发展。该方法可用于诊断患者中的前列腺癌或评估患者对前列腺癌治疗的反应。

2. 发明申请

WO2009153575A1 METHODS OF AIDING IN THE DIAGNOSIS OF PROSTATE CANCER 审中-公开
标题翻译：在前列腺癌诊断中的辅助方法
公开(公告)号：WO2009153575A1
公开(公告)日：2009-12-23
申请号：PCT/GB2009/001556
申请日：2009-06-19
申请人： IMPERIAL INNOVATIONS LIMITED , BULUWELA, Laki , WAXMAN, Jonathan , ALI, Simak , NGAN, Sarah
发明人： BULUWELA, Laki , WAXMAN, Jonathan , ALI, Simak , NGAN, Sarah
IPC分类号： C12Q1/68 , G01N33/00
CPC分类号： G01N33/57434 , A61K31/00 , A61K31/167 , A61K31/519 , A61K31/7076 , A61K31/7088 , A61K45/06 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136 , C12Q2600/154 , C12Q2600/158 , G01N2333/91017 , A61K2300/00
摘要： The current invention provides a method for aiding in the assessment of prostate cancer (including metastatic prostate cancer) and/or benign prostate hyperplasia in a patient, wherein the method comprises the step of determining the level of Glycine N- methyltransferase (GNMT) nucleic acid and/or protein in a sample from the patient. The invention also provides compounds that target Glycine N-methyltransferase (GNMT) protein and/or nucleic acid for use in treating prostate cancer. Also provided are screening methods for selecting a compound considered to be useful in treating prostate cancer, comprising the steps of determining the ability of a test compound to reduce GNMT activity and selecting a compound that reduces GNMT activity. The invention also provides methods for aiding in the diagnosis of prostate cancer in a patient comprising obtaining a sample from the patient and assessing said sample for a marker of GNMT activity.
摘要翻译：本发明提供了一种帮助评估患者前列腺癌（包括转移性前列腺癌）和/或良性前列腺增生的方法，其中该方法包括测定甘氨酸N-甲基转移酶（GNMT）核酸水平的步骤和/或来自患者的样品中的蛋白质。本发明还提供靶向用于治疗前列腺癌的甘氨酸N-甲基转移酶（GNMT）蛋白和/或核酸的化合物。还提供了用于选择被认为可用于治疗前列腺癌的化合物的筛选方法，包括确定测试化合物降低GNMT活性并选择降低GNMT活性的化合物的能力的步骤。本发明还提供了用于帮助诊断患者中前列腺癌的方法，包括从患者获得样品并评估所述样品以获得GNMT活性标志物。

3. 发明申请

WO2003033701A1 CONTROL OF GENE EXPRESSION USING A COMPLEX OF AN OLIGONUCLEOTIDE AND A REGULATORY PEPTIDE 审中-公开
标题翻译：使用寡核苷酸和调节肽复合物控制基因表达
公开(公告)号：WO2003033701A1
公开(公告)日：2003-04-24
申请号：PCT/GB2002/004633
申请日：2002-10-11
申请人： GENE EXPRESSION TECHNOLOGIES LIMITED , HART, Stephen , ALI, Simak , PUFONG, Boris, Tumi , PORTER, Andrew, Christopher, George , BULUWELA, Laki , VAINIKKA, Satu , JENKINSON, John, David , KANDA, Patrick
发明人： HART, Stephen , ALI, Simak , PUFONG, Boris, Tumi , PORTER, Andrew, Christopher, George , BULUWELA, Laki , VAINIKKA, Satu , JENKINSON, John, David , KANDA, Patrick
IPC分类号： C12N15/11
CPC分类号： C12N15/113 , A61K38/00 , C07K2319/00 , C12N9/16 , C12N15/63 , C12N2310/15 , C12N2310/3513 , C12Y203/01048
摘要： A method for suppressing the expression of a selected gene in a cell the method comprising introducing into the cell a molecule comprising (1) a nucleic acid binding portion which binds to a site or associated with the selected gene which site is present in a genome and (2) an expression repressor portion, wherein the nucleic acid binding portion comprises an oligonucleotide or oligonucleotide mimic or analogue, and wherein the repressor portion comprises a polypeptide or peptidomimetic. Molecules for use in the methods of the invention are provided. The repressor may be a portion of a histone deacetylase or DNA methylase or polypeptide capable of recruiting a histone deacetylase or DNA methylase.
摘要翻译：一种抑制细胞中所选择的基因表达的方法，包括向细胞中引入分子，所述分子包含（1）核酸结合部分，所述核酸结合部分结合位点或与所选基因相关联，所述基因存在于基因组中，（2）表达阻遏物部分，其中所述核酸结合部分包含寡核苷酸或寡核苷酸模拟物或类似物，并且其中所述阻遏物部分包含多肽或肽模拟物。提供了用于本发明方法的分子。阻遏物可以是能够募集组蛋白脱乙酰酶或DNA甲基化酶的组蛋白脱乙酰酶或DNA甲基化酶或多肽的一部分。

4. 发明申请

WO2003010308A2 CONTROL OF GENE EXPRESSION 审中-公开
标题翻译：控制基因表达
公开(公告)号：WO2003010308A2
公开(公告)日：2003-02-06
申请号：PCT/GB2002/003336
申请日：2002-07-19
申请人： GENE EXPRESSION TECHNOLOGIES LIMITED , BULUWELA, Lakjaya , HOLMES, David , KAMALATI, Tahereh , WAXMAN, Jonathan , ALI, Simak
发明人： BULUWELA, Lakjaya , HOLMES, David , KAMALATI, Tahereh , WAXMAN, Jonathan , ALI, Simak
IPC分类号： C12N15/00
CPC分类号： C12N15/63
摘要： A method of suppressing the expression of a selected endogenous gene in a eukaryotic cell the method comprising introducing into the cell (a) a polypeptide comprising a nucleic acid binding portion which binds to a site at or associated with the selected gene and a modifying portion which comprises a polypeptide or peptidomimetic which is capable of modulating covalent modification of nucleic acid or chromatin, for example a chromatin inactivation portion, or (b) a polynucleotide encoding said polypeptide. The binding of the molecule to nucleic acid may be modulated by a ligand and the molecule may comprise a ligand binding portion. The nucleic acid binding portion may be a nucleic acid binding portion of a nuclear receptor DNA binding protein.
摘要翻译：在真核细胞中抑制所选内源基因表达的方法，所述方法包括将包含核酸结合部分的多肽引入细胞（a），所述核酸结合部分结合于或与之结合的位点所选基因和修饰部分，所述修饰部分包含能够调节核酸或染色质（例如染色质失活部分）的共价修饰的多肽或肽模拟物，或（b）编码所述多肽的多核苷酸。分子与核酸的结合可以由配体调节，并且分子可以包含配体结合部分。核酸结合部分可以是核受体DNA结合蛋白的核酸结合部分。

5. 发明申请

WO2008151304A1 SELECTIVE INHIBITORS FOR CYCLIN-DEPENDENT KINASES 审中-公开
标题翻译：选择性抑制剂用于循环依赖型动物
公开(公告)号：WO2008151304A1
公开(公告)日：2008-12-11
申请号：PCT/US2008/065988
申请日：2008-06-05
申请人： EMORY UNIVERSITY , IMPERIAL COLLEGE OF SCIENCE AND TECHNOLOGY , JOGALEKAR, Ashutosh, S. , SNYDER, James, P. , LIOTTA, Dennis, C. , BARRETT, Anthony, G.m. , COOMBES, Rcds , ALI, Simak , SIWICKA, Aleksandra , BRACKOW, Jan , SCHEIPER, Bodo
发明人： JOGALEKAR, Ashutosh, S. , SNYDER, James, P. , LIOTTA, Dennis, C. , BARRETT, Anthony, G.m. , COOMBES, Rcds , ALI, Simak , SIWICKA, Aleksandra , BRACKOW, Jan , SCHEIPER, Bodo
IPC分类号： A01N43/90 , A61K31/519
CPC分类号： A61K31/519 , C07D487/04
摘要： This invention provides a class of compounds which are useful for specifically inhibiting cyclin-dependent kinases. This class of compounds finds use in treating diseases resulting from inappropriate activity of cyclin-dependent kinases, including cancer, viral infections (e.g., HIV) neurodegenerative disorders (e.g. Alzheimer's disease), and cardiovascular disorders (e.g. atherosclerosis). Moreover, certain members of this class are particularly useful for inhibiting cyclin-dependent kinase 7 and are especially useful for the treatment of breast cancer.
摘要翻译：本发明提供一类可用于特异性抑制细胞周期蛋白依赖性激酶的化合物。这类化合物可用于治疗由细胞周期蛋白依赖性激酶（包括癌症，病毒感染（例如HIV））神经变性疾病（例如阿尔茨海默病）和心血管疾病（例如动脉粥样硬化）的不适当活动引起的疾病。此外，该类的某些成员特别可用于抑制细胞周期蛋白依赖性激酶7，并且特别可用于治疗乳腺癌。

6. 发明申请

WO2005005473A1 METHODS TO MODULATE THE ACTIVITY OF THE OESTROGEN RECEPTOR 审中-公开
标题翻译：调节雌激素受体活性的方法
公开(公告)号：WO2005005473A1
公开(公告)日：2005-01-20
申请号：PCT/GB2003/005355
申请日：2003-12-09
申请人： IMPERIAL COLLEGE INNOVATIONS LIMITED , ALI, Simak
发明人： ALI, Simak
IPC分类号： C07K14/47
CPC分类号： C07K14/4702
摘要： A polypeptide having the amino acid sequence of Seq ID No 1; Figure 1A or an amino acid sequence having at least 45 or 50 % identity with the amino acid sequence of Seq ID No 1 for use in medicine. Use of a compound for modulating, for example a nuclear receptor DNA binding protein, wherein the compound is: (a) the polypeptide ERZFP (SEQ ID No 1; Figure 1A); or, (b) a fragment of the polypeptide ERZPF which binds to the transcription factor, for example a nuclear receptor DNA binding protein; or, (c) a variant of the polypeptide or fragment as defined in (a) or (b) which binds to the transcription factor, for example a nuclear receptor DNA binding protein; or (d) a fusion or derivative of the polypeptide or fragment as defined in (a), (b) or (c) which binds to the transcription factor, for example a nuclear receptor DNA binding protein; or (e) a peptidomimetic of the polypeptide, fragment, variant, fusion or derivative as defined in (a), (b), (c), or (d) which binds to the transcription factor, for example a nuclear receptor DNA binding protein; or, (f) a compound, for example an antibody or antibody fragment which mimics the binding of the polypeptide, fragment, variant, fusion or derivative as defined in (a), (b), (c), or (d) to the transcription factor, for example a nuclear receptor DNA binding protein. A method for identifying a compound which modulates, for example promotes the transcription factor activity of a transcription factor, for example a nuclear receptor DNA binding protein, comprising the steps of: (a) providing the transcription factor, for example a nuclear receptor DNA binding protein or a fragment thereof comprising the AF1 domain for fragment thereof, and a compound as defined above; (b) exposing a test compound to the transcription factor, for example a nuclear receptor DNA binding protein or fragment and/or a compound as defined above; (c) determining whether the test compound modulates, for example inhibits, the ability of the transcription factor, for example a nuclear receptor DNA binding protein or fragment to bind to the compound as defined above; (d) selecting a compound which modulates, for example enhibits, the ability of the transcription factor, for example a nuclear receptor DNA binding protein or fragment to bind to the compound as defined above.
摘要翻译：具有Seq ID No 1的氨基酸序列的多肽; 图1A或与用于药物的Seq ID No 1的氨基酸序列具有至少45或50％同一性的氨基酸序列。化合物用于调节例如核受体DNA结合蛋白的用途，其中所述化合物为：（a）多肽ERZFP（SEQ ID No.1;图1A）; 或（b）结合转录因子的多肽ERZPF的片段，例如核受体DNA结合蛋白; 或（c）如结合转录因子的（a）或（b）所定义的多肽或片段的变体，例如核受体DNA结合蛋白; 或（d）结合转录因子的（a），（b）或（c）中定义的多肽或片段的融合物或衍生物，例如核受体DNA结合蛋白; 或（e）与转录因子结合的（a），（b），（c）或（d）中定义的多肽，片段，变体，融合物或衍生物的拟肽，例如核受体DNA结合蛋白; 或（f）化合物，例如模拟（a），（b），（c）或（d）中定义的多肽，片段，变体，融合物或衍生物与（a），（c）转录因子，例如核受体DNA结合蛋白。用于鉴定调节例如促进转录因子（例如核受体DNA结合蛋白）的转录因子活性的化合物的方法包括以下步骤：（a）提供转录因子，例如核受体DNA结合蛋白质或其片段包含其片段的AF1结构域和如上定义的化合物; （b）将测试化合物暴露于转录因子，例如核受体DNA结合蛋白或片段和/或如上所定义的化合物; （c）确定测试化合物是否调节，例如抑制转录因子的能力，例如核受体DNA结合蛋白或片段结合如上所定义的化合物; （d）选择调节例如抑制转录因子例如核受体DNA结合蛋白或片段与上述化合物结合的能力的化合物。

7. 发明申请

WO2015124941A1 PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE 审中-公开
标题翻译：吡咯并[1,5-A]嘧啶-5,7-二胺化合物作为CDK抑制剂及其治疗用途
公开(公告)号：WO2015124941A1
公开(公告)日：2015-08-27
申请号：PCT/GB2015/050494
申请日：2015-02-20
申请人： CANCER RESEARCH TECHNOLOGY LIMITED , IMPERIAL INNOVATIONS LIMITED
发明人： BONDKE, Alexander , KROLL, Sebastian , BARRETT, Anthony , FUCHTER, Matthew , SLAFER, Brian , ALI, Simak , COOMBES, Charles , SNYDER, James Patrick
IPC分类号： C07D487/04 , A61K31/519 , A61P35/00
CPC分类号： C07D487/04
摘要： The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7- diamine compounds (referred to herein as "PPDA compounds") that, inter alia , inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.
摘要翻译：本发明一般涉及治疗化合物领域。更具体地，本发明涉及特别是抑制（例如，选择性抑制）CDK的某些吡唑并[1,5-a]嘧啶-5,7-二胺化合物（本文称为“PPDA化合物”）， CDK1，CDK2，CDK4，CDK5，CDK6，CDK7，CDK8，CDK9，CDK10，CDK11，CDK12，CDK13等）。本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内都用于抑制CDK的用途; 并治疗疾病，包括：与CDK相关的疾病; 由细胞周期蛋白依赖性激酶（CDK）的不适当活动引起的疾病; 与CDK突变有关的疾病; 与CDK过表达有关的疾病; 与CDK的上游途径激活相关的疾病; 通过抑制CDK改善的疾病; 增生性疾病; 癌症; 病毒感染（包括艾滋病）; 神经变性疾病（包括阿尔茨海默病和帕金森病）; 缺血; 肾脏疾病; 和心血管疾病（包括动脉粥样硬化）。任选地，治疗还包括用另外的活性剂（例如芳香酶抑制剂，抗雌激素，Her2阻断剂，细胞毒性化学治疗剂等）治疗（例如，同时或顺序治疗）

8. 发明授权

EP3107914B1 PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE 有权转让
公开(公告)号：EP3107914B1
公开(公告)日：2019-01-30
申请号：EP15706282.9
申请日：2015-02-20
申请人： CANCER RESEARCH TECHNOLOGY LIMITED , IMPERIAL INNOVATIONS LIMITED , Emory University
发明人： BONDKE, Alexander , KROLL, Sebastian , BARRETT, Anthony , FUCHTER, Matthew , SLAFER, Brian , ALI, Simak , COOMBES, Charles , SNYDER, James Patrick
IPC分类号： C07D487/04 , A61K31/519 , A61P35/00
CPC分类号： C07D487/04 , A61K31/519 , A61P35/04
摘要： Certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds that inhibit cycline dependent kinase (CDK) (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.) are disclosed. Pharmaceutical compositions comprising these compounds, and the use of these compounds and compositions to inhibit CDK; to treat disorders associated with CDK such as those arising from an inappropriate activity, mutation, overexpression, or upstream pathway activation of CDK; or disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections; neurodegenerative disorders; ischaemia; renal diseases; and cardiovascular disorders are also disclosed. Optionally, the treatment further comprises simultaneous or sequential treatment with a further active agent, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.

9. 发明公开

EP3107914A1 PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE 有权转让
标题翻译： - 吡唑并[1,5-a]嘧啶-5,7-二胺化合物作为CDK抑制剂的及其用途THERAPEUTIC
公开(公告)号：EP3107914A1
公开(公告)日：2016-12-28
申请号：EP15706282.9
申请日：2015-02-20
申请人： CANCER RESEARCH TECHNOLOGY LIMITED , IMPERIAL INNOVATIONS LIMITED , Emory University
发明人： BONDKE, Alexander , KROLL, Sebastian , BARRETT, Anthony , FUCHTER, Matthew , SLAFER, Brian , ALI, Simak , COOMBES, Charles , SNYDER, James Patrick
IPC分类号： C07D487/04 , A61K31/519 , A61P35/00
CPC分类号： C07D487/04 , A61K31/519 , A61P35/04
摘要： Certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds that inhibit cycline dependent kinase (CDK) (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.) are disclosed. Pharmaceutical compositions comprising these compounds, and the use of these compounds and compositions to inhibit CDK; to treat disorders associated with CDK such as those arising from an inappropriate activity, mutation, overexpression, or upstream pathway activation of CDK; or disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections; neurodegenerative disorders; ischaemia; renal diseases; and cardiovascular disorders are also disclosed. Optionally, the treatment further comprises simultaneous or sequential treatment with a further active agent, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.

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