Improved cytotoxicity of antitumor compounds deliverable by the LDL pathway

The concept of LDL-based chemotherapy of cancer is based on the fact that many tumors have high LDL requirements. A series of compounds has been synthesized, some of which meet all criteria for such therapy, i.e., they can be reconstituted with LDL, they do not leak out of the reconstituted LDL (rLDL), and they are potent enough to kill cells exclusively via the LDL receptor pathway. Two of these compounds are significantly superior to the best one from our earlier study [Firestone et al. (1984) J. Med. Chem. 27, 1037-1043], being cytotoxic in rLDL at concentrations reasonably attainable in vivo.