Cathepsin B-sensitive dipeptide prodrugs. 1. A model study of structural requirements for efficient release of doxorubicin.
A series of lysosomal protease-sensitive peptides attached to doxorubicin (DOX) was prepared as model substrates for internalizing anticancer immunoconjugates and potential antimetastasis prodrugs. Rates of cathepsin B-mediated release of free drug was measured for each, and human plasma stabilities for representative examples.
Dubowchik
G M
GM
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA.
Firestone
R A
RA
D002401:Cathepsin B / Q000378:metabolism*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D004317:Doxorubicin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D008958:Models, Molecular; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
D004151:Dipeptides; D004337:Drug Carriers; D011355:Prodrugs; D004317:Doxorubicin; D002401:Cathepsin B