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.
Dubowchik
G M
GM
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660, USA.
Firestone
R A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000633:toxicity*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D006224:Cricetinae; D004337:Drug Carriers; D007202:Indicators and Reagents; D008077:Lipoproteins, LDL; D009682:Magnetic Resonance Spectroscopy; D008466:Mechlorethamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000633:toxicity; D015394:Molecular Structure; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007202:Indicators and Reagents; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D008466:Mechlorethamine