Phosphotyrosine phosphatase inhibitors or phosphotyrosine kinase

Abstract

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.