Aldolase antibody activation of prodrugs of potent aldehyde-containing cytotoxics for selective chemotherapy.
Prodrugs of potent aldehyde analogues of the anticancer drug doxorubicin (Dox) were synthesized. These prodrugs were efficiently activated by antibody 93F3 and no drug formation was observed in the absence of 93F3 in either phosphate buffered saline or cell culture media. In the presence of antibody 93F3, these prodrugs were activated and decreased the proliferation of human cancer cells in in vitro proliferation assays.
Sinha
Subhash C
SC
Skaggs Institute for Chemical Biology and Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. subhash@scripps.edu
Li
Lian-Sheng
LS
Watanabe
Shin-Ichi
S
Kaltgrad
Eiton
E
Tanaka
Fujie
F
Rader
Christoph
C
Lerner
Richard A
RA
Barbas
Carlos F
CF
D000447:Aldehydes / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017151:Antibodies, Catalytic / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000447:Aldehydes; D000903:Antibiotics, Antineoplastic; D017151:Antibodies, Catalytic; D007140:Immunoglobulin Fab Fragments; D011355:Prodrugs; D004317:Doxorubicin; C109536:antibody aldolase; D005634:Fructose-Bisphosphate Aldolase