CONJUGATED SURAMIN OR DERIVATIVES THEREOF WITH PEG, POLYASPARTATE OR POLYGLUTAMATE FOR CANCER TREATMENT

摘要

The present invention provides an assay that identifies compounds which inhibit cleavage of HGF/SF by serum proteases such as uPA, and methods in which such compounds are provided to reaction solutions, to cultured cells in vitro, or to a mammal in vivo, to inhibit cleavage of HGF/SF and to inhibit chemical and biological effects resulting from the activation of c-Met receptor by HGF/SF. The invention also provides methods for modifying suramin and suramin-related polysulfonated compounds that inhibit HGF/SF cleavage, by attaching PEG or polyanions such as polyglutamate or polyaspartate to the compounds to reduce cellular uptake of the compounds, thereby reducing their cytotoxicity. Also provided are a pharmaceutical composition containing at least one polysulfonated HGF/SF cleavage-inhibiting compound other than suramin, and a pharmaceutical composition containing at least one HGF/SF cleavage-inhibiting form of suramin or a suramin-related polysulfonated compound that is modified by conjugation to a chemical moiety that reduces uptake of the compound into cells. The present invention further includes methods wherein such pharmaceutical compositions are administered to a mammal with a tumor that is stimulated to grow by HGF/SF, to inhibit the growth or metastasis of the tumor in the mammal.