New hydrazone derivatives of adriamycin and their immunoconjugates--a correlation between acid stability and cytotoxicity.
New N-substituted hydrazine linkers were synthesized and their hydrazone derivatives of adriamycin were prepared. These functionalized adriamycin derivatives were conjugated with a monoclonal antibody, 5E9. The release rate of adriamycin from the hydrazones and from some of the conjugates was studied, and their relationship to the IC50's of the conjugate against 5E9-positive Daudi cells was investigated.
Kaneko
T
T
Bristol-Myers Squibb Company, Wallingford, Connecticut 06492-7660.
Willner
D
D
Monkovíc
I
I
Knipe
J O
JO
Braslawsky
G R
GR
Greenfield
R S
RS
Vyas
D M
DM
D000911:Antibodies, Monoclonal / Q000737:chemistry; D002051:Burkitt Lymphoma / Q000188:drug therapy; D003432:Cross-Linking Reagents / Q000138:chemical synthesis*; D003602:Cytotoxicity, Immunologic; D004317:Doxorubicin / Q000031:analogs & derivatives*; D004355:Drug Stability; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D000922:Immunotoxins; D007700:Kinetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D006835:Hydrazones; D000922:Immunotoxins; D004317:Doxorubicin