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    Phosphotyrosine phosphatase inhibitors or phosphotyrosine kinase activators for controlling cellular proliferation
    3.
    发明授权
    Phosphotyrosine phosphatase inhibitors or phosphotyrosine kinase activators for controlling cellular proliferation 失效
    磷酸酪氨酸磷酸酶抑制剂或磷酸酪氨酸激酶激活剂用于控制细胞增殖

    公开(公告)号：US5877210A

    公开(公告)日：1999-03-02

    申请号：US465813

    申请日：1995-06-05

    申请人： Gary L. Schieven

    发明人： Gary L. Schieven

    IPC分类号： A61K31/555 ,  A61K31/66 ,  A61K41/00 ,  A61K47/48 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P37/06 ,  C07F9/00 ,  C07F11/00 ,  A01N55/02 ,  A61K39/395 ,  C07F53/00

    CPC分类号： A61K31/661 ,  A61K31/555 ,  A61K31/66 ,  A61K31/662 ,  A61K31/664 ,  A61K31/683 ,  A61K41/0038 ,  A61K47/48276 ,  C07F9/005

    摘要： A method of inhibiting the proliferation of B cells by using inhibitors of phosphotyrosine phosphatase can be used to regulate the immune response and to treat diseases such as leukemias or lymphomas marked by malignant proliferation of B cells or T cells. Antitumor activity is seen in vivo against tumors and against tumor cell lines. The use of such inhibitors can be combined with radiation, which produces a synergistic effect. Several types of inhibitors can be used, including: (1) compounds comprising a metal coordinate-covalently bound to an organic moiety that can form a five- or six-membered ring, in which the metal is preferably vanadium (IV); (2) compounds in which vanadium (IV) is coordinate-covalently bound to an organic moiety such as a hydroxamate, .alpha.-hydroxypyridinone, .alpha.-hydroxypyrone, .alpha.-amino acid, hydroxycarbonyl, or thiohydroxamate; (3) coordinate-covalent complexes of vanadyl and cysteine or a derivative thereof; (4) nonhydrolyzable phosphotyrosine phosphatase analogues; (5) dephostatin; (6) 4-(fluoromethyl)phenyl phosphate and esterified derivatives; and (7) coordinate-covalent metal-organic compounds containing at least one oxo or peroxo ligand bound to the metal, in which the metal is preferably vanadium (V), molybdenum (VI), or tungsten (VI). Methods of stimulating signaling in T cells and conjugates of a modulator of phosphotyrosine metabolism with a specific binding partner for a B cell surface antigen are also disclosed.

    摘要翻译： 可以使用通过使用磷酸酪氨酸磷酸酶抑制剂抑制B细胞增殖的方法来调节免疫应答并治疗由B细胞或T细胞的恶性增殖标记的白血病或淋巴瘤等疾病。 体内抗肿瘤活性和抗肿瘤细胞系。 这种抑制剂的使用可以与辐射组合，这产生协同效应。 可以使用几种类型的抑制剂，包括：（1）包含与可形成五元或六元环的有机部分共价键合的金属的化合物，其中金属优选为钒（IV）; （2）其中钒（IV）与有机部分如羟肟酸盐，α-羟基吡啶酮，α-羟基吡喃酮，α-氨基酸，羟基羰基或硫代羟基肟酸共价键合的化合物; （3）氧钒和半胱氨酸的配位共价络合物或其衍生物; （4）不可水解的磷酸酪氨酸磷酸酶类似物; （5）dephostatin; （6）4-（氟甲基）苯基磷酸酯和酯化衍生物; 和（7）含有至少一个与金属结合的氧代或过氧配体的配位共价金属有机化合物，其中金属优选为钒（V），钼（VI）或钨（VI）。 还公开了在T细胞中刺激信号的方法和磷酸酪氨酸代谢调节剂与B细胞表面抗原的特异性结合配偶体的缀合物的方法。

    Use of phosphotyrosine phosphatase inhibitors or phosphotyrosine kinase activators for controlling cellular proliferation
    4.
    发明授权
    Use of phosphotyrosine phosphatase inhibitors or phosphotyrosine kinase activators for controlling cellular proliferation 失效
    使用磷酸酪氨酸磷酸酶抑制剂或磷酸酪氨酸激酶激活剂来控制细胞增殖

    公开(公告)号：US5846998A

    公开(公告)日：1998-12-08

    申请号：US669499

    申请日：1996-06-18

    申请人： Gary L. Schieven

    发明人： Gary L. Schieven

    IPC分类号： A61K31/555 ,  A61K31/66 ,  A61K41/00 ,  A61K47/48 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P37/06 ,  C07F9/00 ,  C07F11/00 ,  A01N55/02 ,  A01N59/16 ,  C12N9/99

    CPC分类号： A61K31/661 ,  A61K31/555 ,  A61K31/66 ,  A61K31/662 ,  A61K31/664 ,  A61K31/683 ,  A61K41/0038 ,  A61K47/48276 ,  C07F9/005

    摘要： A method of inhibiting the proliferation of B cells by using inhibitors of phosphotyrosine phosphatase can be used to regulate the immune response and to treat diseases such as leukemias or lymphomas marked by malignant proliferation of B cells or T cells. Antitumor activity is seen in vivo against tumors and against tumor cell lines. The use o such inhibitors can be combined with radiation, which produces a synergistic effect. Several types of inhibitors can be used, including: (1) compounds comprising a metal coordinate-covalently bound to an organic moiety that can form a five- or six-membered ring, in which the metal is preferably vanadium (IV); (2) compounds in which vanadium (IV) is coordinate-covalently bound to an organic moiety such as a hydroxamate, .alpha.-hydroxypyridinone, .alpha.-hydroxypyrone, .alpha.-amino acid, hydroxycarbonyl, or thiohydroxamate; (3) coordinate-covalent complexes of cysteine or a derivative thereof; (4) nonhydrolyzable phosphotyrosine analogues; (5) dephostatin; (6) 4-(fluoromethyl)phenyl phosphate and esterified derivatives; and (7) coordinate-covalent metal-organic compounds containing at least one oxo or peroxo ligand bound to the metal, in which the metal is preferably vanadium (V), molybdenum (VI), or tungsten (VI).

    摘要翻译： PCT No.PCT / US95 / 01234 Sec。 371日期1996年6月18日 102（e）1996年6月18日PCT 1995年1月30日PCT PCT。 公开号WO95 / 20390 日期1995年8月3日通过使用磷酸酪氨酸磷酸酶抑制剂抑制B细胞增殖的方法可用于调节免疫应答并治疗由B细胞或T细胞恶性增殖标记的白血病或淋巴瘤等疾病。 体内抗肿瘤活性和抗肿瘤细胞系。 这种抑制剂的使用可以与辐射组合，这产生协同效应。 可以使用几种类型的抑制剂，包括：（1）包含与可形成五元或六元环的有机部分共价键合的金属的化合物，其中金属优选为钒（IV）; （2）其中钒（IV）与有机部分如羟肟酸盐，α-羟基吡啶酮，α-羟基吡喃酮，α-氨基酸，羟基羰基或硫代羟基肟酸共价键合的化合物; （3）半胱氨酸或其衍生物的配位共价复合物; （4）不可水解的磷酸酪氨酸类似物; （5）dephostatin; （6）4-（氟甲基）苯基磷酸酯和酯化衍生物; 和（7）含有与金属结合的至少一个氧代或过氧配体的配位共价金属有机化合物，其中金属优选为钒（V），钼（VI）或钨（VI）。

    Use of phosphotyrosine phosphatase inhibitors for controlling cellular proliferation
    5.
    发明授权
    Use of phosphotyrosine phosphatase inhibitors for controlling cellular proliferation 失效
    磷酸酪氨酸磷酸酶抑制剂用于控制细胞增殖

    公开(公告)号：US5693627A

    公开(公告)日：1997-12-02

    申请号：US450401

    申请日：1995-05-25

    申请人： Gary L. Schieven

    发明人： Gary L. Schieven

    IPC分类号： A61K31/555 ,  A61K31/66 ,  A61K41/00 ,  A61K47/48 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P37/06 ,  C07F9/00 ,  C07F11/00 ,  C07F9/02 ,  C12N1/38 ,  C12N9/99

    CPC分类号： A61K31/661 ,  A61K31/555 ,  A61K31/66 ,  A61K31/662 ,  A61K31/664 ,  A61K31/683 ,  A61K41/0038 ,  A61K47/48276 ,  C07F9/005

    摘要： A method of inhibiting the proliferation of B cells by using inhibitors of phosphotyrosine phosphatase can be used to regulate the immune response and to treat diseases such as leukemias or lymphomas marked by malignant proliferation of B cells. The use of such inhibitors can be combined with radiation, which produces a synergistic effect. Several types of inhibitors can be used, including: (1) compounds comprising a metal coordinate-covalently bound to an organic moiety that can form a five- or six-membered ring; (2) compounds in which vanadium (IV) is coordinate-covalently bound to an organic moiety such as a hydroxamate, .alpha.-hydroxypyridinone, .alpha.-hydroxypyrone, .alpha.-amino acid, hydroxycarbonyl, or thiohydroxamate; (3) coordinate-covalent complexes of vanadyl and cysteine or a derivative thereof; (4) nonhydrolyzable phosphotyrosine phosphatase analogues; (5) phostatin; and (6) 4-(fluoromethyl)phenyl phosphate and esterified derivatives. For the metal-containing coordinate covalent compounds, the metal is preferably vanadium (IV).

    摘要翻译： 可以使用通过使用磷酸酪氨酸磷酸酶抑制剂抑制B细胞增殖的方法来调节免疫应答并治疗由B细胞的恶性增殖标记的白血病或淋巴瘤等疾病。 这种抑制剂的使用可以与辐射组合，这产生协同效应。 可以使用几种类型的抑制剂，包括：（1）包含与可形成五元或六元环的有机部分共价键合的金属的化合物; （2）其中钒（IV）与有机部分如羟肟酸盐，α-羟基吡啶酮，α-羟基吡喃酮，α-氨基酸，羟基羰基或硫代羟基肟酸共价键合的化合物; （3）氧钒和半胱氨酸的配位共价络合物或其衍生物; （4）不可水解的磷酸酪氨酸磷酸酶类似物; （5）光抑制素 和（6）4-（氟甲基）苯基磷酸酯和酯化衍生物。 对于含金属的配位共价化合物，金属优选为钒（IV）。

    Use of phosphotyrosine phospatase inhibitors for controlling cellular proliferation
    7.
    发明授权
    Use of phosphotyrosine phospatase inhibitors for controlling cellular proliferation 失效
    磷酸酪氨酸磷酸酶抑制剂用于控制细胞增殖

    公开(公告)号：US5565491A

    公开(公告)日：1996-10-15

    申请号：US189330

    申请日：1994-01-31

    申请人： Gary L. Schieven

    发明人： Gary L. Schieven

    IPC分类号： A61K31/555 ,  A61K31/66 ,  A61K41/00 ,  A61K47/48 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P37/06 ,  C07F9/00 ,  C07F11/00 ,  A61K31/28 ,  A61K31/30 ,  C07F1/08 ,  C07F5/00

    CPC分类号： A61K31/661 ,  A61K31/555 ,  A61K31/66 ,  A61K31/662 ,  A61K31/664 ,  A61K31/683 ,  A61K41/0038 ,  A61K47/48276 ,  C07F9/005

    摘要： A method of inhibiting the proliferation of B cells by using inhibitors of phosphotyrosine phosphatase can be used to regulate the immune response and to treat diseases such as leukemias or lymphomas marked by malignant proliferation of B cells. The use of such inhibitors can be combined with radiation, which produces a synergistic effect. Several types of inhibitors can be used, including: (1) compounds comprising a metal coordinate-covalently bound to an organic moiety that can form a five- or six-membered ring; (2) compounds in which vanadium (IV) is coordinate-covalently bound to an organic moiety such as a hydroxamate, .alpha.-hydroxypyridinone, .alpha.-hydroxypyrone, .alpha.-amino acid, hydroxycarbonyl, or thiohydroxamate; (3) coordinate-covalent complexes of vanadyl and cysteine or a derivative thereof; (4) nonhydrolyzable phosphotyrosine phosphatase analogues; (5) phostatin; and (6) 4-(fluoromethyl)phenyl phosphate and esterified derivatives. For the metal-containing coordinate covalent compounds, the metal is preferably vanadium (IV).

    摘要翻译： 可以使用通过使用磷酸酪氨酸磷酸酶抑制剂抑制B细胞增殖的方法来调节免疫应答并治疗由B细胞的恶性增殖标记的白血病或淋巴瘤等疾病。 这种抑制剂的使用可以与辐射组合，这产生协同效应。 可以使用几种类型的抑制剂，包括：（1）包含与可形成五元或六元环的有机部分共价键合的金属的化合物; （2）其中钒（IV）与有机部分如羟肟酸盐，α-羟基吡啶酮，α-羟基吡喃酮，α-氨基酸，羟基羰基或硫代羟基肟酸共价键合的化合物; （3）氧钒和半胱氨酸的配位共价络合物或其衍生物; （4）不可水解的磷酸酪氨酸磷酸酶类似物; （5）光抑制素 和（6）4-（氟甲基）苯基磷酸酯和酯化衍生物。 对于含金属的配位共价化合物，金属优选为钒（IV）。