Patent ID: 7833737

Claim:
A diagnostic/prognostic method for a preneoplastic/neoplastic disease associated with abnormal MN/CA IX expression, comprising determining whether MN/CA IX is activated in a vertebrate sample, comprising: (a) determining whether MN/CA IX is overexpressed in said vertebrate sample, at a level above that for a control sample; and if so, (b) contacting said vertebrate sample with a membrane-impermeant, potent specific inhibitor of activated MN/CA IX, wherein said membrane-impermeant, potent specific inhibitor of activated MN/CA IX is selected from the group consisting of organic heterocyclic sulfonamides and aromatic sulfonamides, and (c) detecting or detecting and quantifying binding of said specific inhibitor of activated MN/CA IX in said vertebrate sample; wherein binding of said inhibitor to MN/CA IX indicates that MN/CA IX is activated; wherein said inhibitor of activated MN/CA IX is determined to be a potent inhibitor of MN/CA IX enzymatic activity in a screening assay comprising determining the inhibition constant K I , of said inhibitor, wherein if said inhibition constant K I , is determined to be less than about 50 nanomolar, said inhibitor of activated MN/CA IX is determined to be a potent inhibitor of MN/CA IX enzymatic activity; wherein said inhibitor of activated MN/CA IX is determined to be an MN/CA IX-specific inhibitor if said inhibitor is a more potent inhibitor of MN/CA IX enzymatic activity than of the enzymatic activity of at least one of the carbonic anhydrases selected from the group consisting of CA I, CA II and CA IV; and wherein said potent inhibitor of activated MN/CA IX is considered to be membrane-impermeant if it is tested in a membrane permeance assay comprising: (1) incubating a millimolar solution of said potent inhibitor of activated MN/CA IX with human erythrocytes at 37° C. for at least 30 minutes; (2) washing said human erythrocytes; (3) quantitating the levels of said potent inhibitor present in said human erythrocytes; and (4) if said potent inhibitor is present in said human erythrocytes at 1 micromolar or less, then said potent inhibitor is considered to be membrane-impermeant.