Synthesis of potent taxoids for tumor-specific delivery using monoclonal antibodies.
The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prepared to investigate the most suitable position for conjugation. A second series of taxoids modified at the C-2 position aimed at increasing the potency of these taxanes has also been prepared.
Miller
Michael L
ML
ImmunoGen, Inc., 128 Sidney Street, Cambridge, MA 02139, USA. michael.miller@immunogen.com
Roller
Elizabeth E
EE
Wu
Xinyaun
X
Leece
Barbara A
BA
Goldmacher
Victor S
VS
Chari
Ravi V J
RV
Ojima
Iwao
I
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D016503:Drug Delivery Systems; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D017239:Paclitaxel / Q000633:toxicity; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis* / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D043823:Taxoids; D017239:Paclitaxel