| 摘要 |
The present invention provides pharmaceutical compositions comprising phosphaplatins, stable isolated monomeric phosphato complexes of platinum (II) and (IV). In some embodiments, such compositions may be useful for treating cancers, including cisplatin- and carboplatin-resistant cancers. The provided phosphaplatin complexes do not readily undergo hydrolysis and are quite soluble and stable in aqueous solutions. Moreover, these complexes-unlike cisplatin, carboplatin, and related platinum-based agents-do not bind DNA. Rather, data suggests that phosphaplatins trigger overexpression of fas and fas-related transcription factors and some proapoptotic genes such as Bak and Bax. Nevertheless, the complexes exhibit tremendous cytotoxicity towards cancer cells. Thus, the present invention provides novel platinum agents that have a different molecular target than those in the art. |
