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    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof
    4.
    发明授权
    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof 失效
    荧光或荧光报告分子及其在半胱氨酸蛋白酶和其他酶的全细胞荧光筛选测定中的应用及其用途

    公开(公告)号：US07270801B2

    公开(公告)日：2007-09-18

    申请号：US10829381

    申请日：2004-04-22

    申请人： Eckard Weber ,  Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    发明人： Eckard Weber ,  Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    IPC分类号： A61N49/00

    CPC分类号： G01N15/1456 ,  C12Q1/68 ,  G01N33/533 ,  G01N2015/1006 ,  G01N2015/1488 ,  Y10S436/80

    摘要： The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

    摘要翻译： 本发明涉及新的荧光染料，新的荧光和荧光报道分子和新的酶测定方法，其可用于检测来自任何活生物体的全细胞，细胞系和组织样品中参与细胞凋亡的半胱天冬酶和其它酶的活性 或器官。 报告分子和测定方法可以用于药物筛选程序中，以鉴定在整个细胞或组织中作为半胱天冬酶级联的抑制剂或诱导剂的化合物。 本文所述的试剂和测定法也可用于确定人类癌细胞对用化学治疗药物治疗的化学敏感性。 本发明还涉及可用于检测2型甲硫氨酸氨基肽酶，二肽基肽酶IV，钙蛋白酶，氨基肽酶，HIV蛋白酶，腺病毒蛋白酶，HSV-1蛋白酶的活性的新型荧光和荧光报告分子和新的酶测定方法， HCMV蛋白酶和HCV蛋白酶。

    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for capsases and other enzymes and the use thereof
    5.
    发明授权
    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for capsases and other enzymes and the use thereof 失效
    荧光或荧光报道分子及其在全酶抑制剂中的应用及其用途

    公开(公告)号：US06342611B1

    公开(公告)日：2002-01-29

    申请号：US09168888

    申请日：1998-10-09

    申请人： Eckard Weber ,  Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    发明人： Eckard Weber ,  Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    IPC分类号： C07D31188

    CPC分类号： G01N15/1456 ,  C12Q1/68 ,  G01N33/533 ,  G01N2015/1006 ,  G01N2015/1488 ,  Y10S436/80

    摘要： The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

    摘要翻译： 本发明涉及新的荧光染料，新的荧光和荧光报道分子和新的酶测定方法，其可用于检测来自任何活生物体的全细胞，细胞系和组织样品中参与细胞凋亡的半胱天冬酶和其它酶的活性 或器官。 报告分子和测定方法可以用于药物筛选程序中，以鉴定在整个细胞或组织中作为半胱天冬酶级联的抑制剂或诱导剂的化合物。 本文所述的试剂和测定法也可用于确定人类癌细胞对用化学治疗药物治疗的化学敏感性。 本发明还涉及可用于检测2型甲硫氨酸氨基肽酶，二肽基肽酶IV，钙蛋白酶，氨基肽酶，HIV蛋白酶，腺病毒蛋白酶，HSV-1蛋白酶的活性的新型荧光和荧光报告分子和新的酶测定方法， HCMV蛋白酶和HCV蛋白酶。

    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof
    6.
    发明授权
    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof 失效
    荧光或荧光报告分子及其在半胱氨酸蛋白酶和其他酶的全细胞荧光筛选测定中的应用及其用途

    公开(公告)号：US06759207B2

    公开(公告)日：2004-07-06

    申请号：US09947387

    申请日：2001-09-07

    申请人： Eckard Weber ,  Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    发明人： Eckard Weber ,  Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    IPC分类号： G01N33573

    CPC分类号： G01N15/1456 ,  C12Q1/68 ,  G01N33/533 ,  G01N2015/1006 ,  G01N2015/1488 ,  Y10S436/80

    摘要： The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

    摘要翻译： 本发明涉及新的荧光染料，新的荧光和荧光报道分子和新的酶测定方法，其可用于检测来自任何活生物体的全细胞，细胞系和组织样品中参与细胞凋亡的半胱天冬酶和其它酶的活性 或器官。 报告分子和测定方法可以用于药物筛选程序中，以鉴定在整个细胞或组织中作为半胱天冬酶级联的抑制剂或诱导剂的化合物。 本文所述的试剂和测定法也可用于确定人类癌细胞对用化学治疗药物治疗的化学敏感性。 本发明还涉及可用于检测2型甲硫氨酸氨基肽酶，二肽基肽酶IV，钙蛋白酶，氨基肽酶，HIV蛋白酶，腺病毒蛋白酶，HSV-1蛋白酶的活性的新型荧光和荧光报告分子和新的酶测定方法， HCMV蛋白酶和HCV蛋白酶。

    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof
    7.
    发明授权
    Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof 有权
    荧光或荧光报告分子及其在半胱氨酸蛋白酶和其他酶的全细胞荧光筛选测定中的应用及其用途

    公开(公告)号：US06335429B1

    公开(公告)日：2002-01-01

    申请号：US09521650

    申请日：2000-03-08

    申请人： Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    发明人： Sui Xiong Cai ,  John F. W. Keana ,  John A. Drewe ,  Han-Zhong Zhang

    IPC分类号： C07K1702

    CPC分类号： G01N15/1456 ,  C12Q1/68 ,  G01N33/533 ,  G01N2015/1006 ,  G01N2015/1488 ,  Y10S436/80

    摘要： The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

    摘要翻译： 本发明涉及新的荧光染料，新的荧光和荧光报道分子和新的酶测定方法，其可用于检测来自任何活生物体的全细胞，细胞系和组织样品中参与细胞凋亡的半胱天冬酶和其它酶的活性 或器官。 报告分子和测定方法可以用于药物筛选程序中，以鉴定在整个细胞或组织中作为半胱天冬酶级联的抑制剂或诱导剂的化合物。 本文所述的试剂和测定法也可用于确定人类癌细胞对用化学治疗药物治疗的化学敏感性。 本发明还涉及可用于检测2型甲硫氨酸氨基肽酶，二肽基肽酶IV，钙蛋白酶，氨基肽酶，HIV蛋白酶，腺病毒蛋白酶，HSV-1蛋白酶的活性的新型荧光和荧光报告分子和新的酶测定方法， HCMV蛋白酶和HCV蛋白酶。

    Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof
    10.
    发明授权
    Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof 有权
    碳环和杂环取代的缩氨基脲和缩氨基硫脲和其用途

    公开(公告)号：US06458843B1

    公开(公告)日：2002-10-01

    申请号：US09421403

    申请日：1999-10-21

    申请人： Yan Wang ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana ,  Victor I. Ilyin ,  Eckard Weber

    发明人： Yan Wang ,  Sui Xiong Cai ,  Nancy C. Lan ,  John F. W. Keana ,  Victor I. Ilyin ,  Eckard Weber

    IPC分类号： A61K3117

    CPC分类号： C07D213/643 ,  A61K31/17 ,  A61K31/175 ,  A61K31/44 ,  A61K31/445 ,  A61K31/47 ,  A61K31/505 ,  C07C281/12 ,  C07C281/14 ,  C07C2601/14 ,  C07D209/14 ,  C07D211/46 ,  C07D213/68 ,  C07D215/12 ,  C07D307/91 ,  C07D309/12 ,  C07D317/50 ,  C07D317/58 ,  C07D317/62 ,  C07D317/64 ,  C07D319/18

    摘要： This invention is related to carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones represented by Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein: Y is oxygen or sulfur; R1, R21, R22 and R23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; or R22 and R23, together with the N, form a heterocycle; A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one or O, S, NR24, CR25R26, C(O), NR24C(O), C(O)NR24, SO, SO2 or a covalent bond; where R24, R25 and R26 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl. The invention also is directed to the use of carbocycle and heterocycle substituted semicarbazones and thiosemicarbazones for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), for the treatment and prevention of otoneurotoxicity and eye diseases involving glutamate toxicity and for the treatment, prevention or amelioration of pain, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy and urinary incontinence.

    摘要翻译： 本发明涉及由式I表示的碳环和杂环取代的缩氨基脲和缩氨基硫脲或其药学上可接受的盐或前药，其中：Y是氧或硫; R1，R21，R22和R23独立地是氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基; 或R 22和R 23与N一起形成杂环; A1和A2独立地是芳基，杂芳基，饱和或部分不饱和的碳环或饱和或部分不饱和的杂环，其中任何一个任选被取代; X是1或O，S，NR 24，CR 25 R 26，C（O），NR 24 C（O），C（O）NR 24，SO，SO 2或共价键; 其中R 24，R 25和R 26独立地是氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基。 本发明还涉及使用碳环和杂环取代的缩氨基脲和缩氨基硫脲来治疗全身和局部缺血后的神经元损伤，用于治疗或预防神经变性疾病如肌萎缩性侧索硬化（ALS），用于治疗和预防 涉及谷氨酸毒性和治疗，预防或改善疼痛，作为抗惊厥药，以及作为局部麻醉剂，作为抗心律失常药物和用于治疗或预防糖尿病性神经病和尿失禁的抗疟药抑制剂。