Cathepsin B-sensitive dipeptide prodrugs. 2. Models of anticancer drugs paclitaxel (Taxol), mitomycin C and doxorubicin.
Substrates containing doxorubicin (DOX), paclitaxel (taxol), and mitomycin C (MMC) attached to the cathepsin B-sensitive dipeptide Phe-Lys via a self-immolative spacer were prepared as model compounds for internalizing anticancer immunoconjugates. Cathepsin B-mediated release rates of free drug, rat liver lysosomal susceptibility and human plasma stability were measured for each.
Dubowchik
G M
GM
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA.
Mosure
K
K
Knipe
J O
JO
Firestone
R A
RA
D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000138:chemical synthesis*; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D016685:Mitomycin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats
D004151:Dipeptides; D004337:Drug Carriers; D011355:Prodrugs; D016685:Mitomycin; D004317:Doxorubicin; D002401:Cathepsin B; D017239:Paclitaxel