公开(公告)号：US5919775A

公开(公告)日：1999-07-06

申请号：US61286

申请日：1998-04-16

申请人： Ashok R. Amin ,  Steven B. Abramson ,  Lorne M. Golub ,  Nungavaram S. Ramamurthy ,  Thomas F. McNamara ,  Robert A. Greenwald ,  Howard Trachtman

发明人： Ashok R. Amin ,  Steven B. Abramson ,  Lorne M. Golub ,  Nungavaram S. Ramamurthy ,  Thomas F. McNamara ,  Robert A. Greenwald ,  Howard Trachtman

IPC分类号： A61K31/65 ,  A61P13/12 ,  A61P19/02 ,  A61P29/00 ,  A61P43/00

CPC分类号： A61K31/65

摘要： The invention is a method of inhibiting the production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo biological system. The method employs a tetracycline compound to inhibit the production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the biological system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

摘要翻译： 本发明是一种在体内，体外或离体生物体系中抑制一氧化氮（NO）的产生的方法。 该方法采用四环素化合物抑制NO的产生和/或抑制一氧化氮合酶（iNOS）的诱导型异构体的表达或活性。 优选地，四环素化合物对金属蛋白酶具有抑制活性。 此外，优选的是，四环素化合物以系统中几乎没有或没有抗菌活性的量提供给生物系统。 因此，优选的四环素化合物是四环素化合物，其被修饰以降低或消除其抗微生物活性。 该方法可用于治疗以iNOS介导的NO产生为特征的哺乳动物的医疗状况，包括例如炎性病症。

公开(公告)号：US5789395A

公开(公告)日：1998-08-04

申请号：US697815

申请日：1996-08-30

申请人： Ashok R. Amin ,  Steven B. Abramson ,  Lorne M. Golub ,  Nungavaram S. Ramamurthy ,  Thomas F. McNamara ,  Robert A. Greenwald ,  Howard Trachtman

发明人： Ashok R. Amin ,  Steven B. Abramson ,  Lorne M. Golub ,  Nungavaram S. Ramamurthy ,  Thomas F. McNamara ,  Robert A. Greenwald ,  Howard Trachtman

IPC分类号： A61K31/65 ,  A61P13/12 ,  A61P19/02 ,  A61P29/00 ,  A61P43/00 ,  C12N9/99 ,  C12N9/04 ,  C12N9/06

CPC分类号： A61K31/65

摘要： A method is disclosed for inhibiting endogenous production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo mammalian system. The method employs a tetracycline compound to inhibit production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the mammalian system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

摘要翻译： 公开了用于抑制体内，体外或离体哺乳动物系统中一氧化氮（NO）的内源性产生的方法。 该方法采用四环素化合物抑制NO的产生和/或抑制一氧化氮合酶（iNOS）的诱导型亚型的表达或活性。 优选地，四环素化合物对金属蛋白酶具有抑制活性。 此外，优选的是，四系环化合物以系统中几乎没有或没有抗菌活性的量提供给哺乳动物系统。 因此，优选的四环素化合物是四环素化合物，其被修饰以降低或消除其抗微生物活性。 该方法可用于治疗以iNOS介导的NO产生为特征的哺乳动物的医疗状况，包括例如炎性病症。

公开(公告)号：US5759836A

公开(公告)日：1998-06-02

申请号：US410739

申请日：1995-03-27

申请人： Ashok R. Amin ,  Steven B. Abramson

发明人： Ashok R. Amin ,  Steven B. Abramson

IPC分类号： C12N9/02 ,  C12Q1/26 ,  C12N9/99

CPC分类号： C12N9/0075 ,  C12Q1/26

摘要： An novel isoform of inducible nitric oxide synthase (OA-NOS) has been identified in osteoarthritis-affected articular cartilage. Some properties, including molecular weight, are similar to the constitutive isoform of neuronal nitric oxide synthase (ncnos) while other properties share similarity with the previously identified inducible nitric oxide (iNOS). Acetylating agents, such as aspirin and N-acetylimidazole act on both iNOS and OA-NOS by inhibiting their catalytic activities. A method is provided to screen for acetylating agents that inhibit OA-NOS, and the selective inhibition of OA-NOS by inhibitory agents is determined by comparison to a panel of different isoforms of nitric oxide synthase.

摘要翻译： 在骨关节炎患者的关节软骨中已经鉴定出诱导型一氧化氮合酶（OA-NOS）的新型同工型。 一些性质，包括分子量，类似于神经元一氧化氮合酶（ncnos）的组成型，而其他性质与先前鉴定的诱导型一氧化氮（iNOS）具有相似性。 乙酰化剂如阿司匹林和N-乙酰咪唑通过抑制其催化活性而作用于iNOS和OA-NOS。 提供了筛选抑制OA-NOS的乙酰化剂的方法，并且通过与一组不同同种型的一氧化氮合酶的比较来确定通过抑制剂对OA-NOS的选择性抑制。