TY - JOUR
T1 - Design and tumor targeting of anthracyclines able to overcome multidrug resistance
T2 - A double-advantage approach
AU - Priebe, Waldemar
AU - Perez-Soler, Roman
PY - 1993
Y1 - 1993
N2 - A novel 'double-advantage approach' to developing more effective chemotherapies will be reviewed. This approach is based on a presumption that analogs designed on a sound hypothesis, and combined with a rationally selected drug delivery system, will optimize antitumor activity by creating drugs that are more active and that can be more specifically targeted to tumors. In the design of drugs superior to doxorubicin, we have focused on typical multidrug resistance and new anthracycline analogs, whose uptake is not affected by P-glycoprotein. Analysis of structural elements of anthracyclines affecting activity against multidrug resistant tumors and affinity for liposomes will be discussed. Annamycin, a lipophilic anthracycline analog, was selected for further preclinical development as a liposomal formulation and demonstrated, in the initial biological evaluation, high activity against tumors resistant to doxorubicin.
AB - A novel 'double-advantage approach' to developing more effective chemotherapies will be reviewed. This approach is based on a presumption that analogs designed on a sound hypothesis, and combined with a rationally selected drug delivery system, will optimize antitumor activity by creating drugs that are more active and that can be more specifically targeted to tumors. In the design of drugs superior to doxorubicin, we have focused on typical multidrug resistance and new anthracycline analogs, whose uptake is not affected by P-glycoprotein. Analysis of structural elements of anthracyclines affecting activity against multidrug resistant tumors and affinity for liposomes will be discussed. Annamycin, a lipophilic anthracycline analog, was selected for further preclinical development as a liposomal formulation and demonstrated, in the initial biological evaluation, high activity against tumors resistant to doxorubicin.
KW - Antitumor agents
KW - anamycin
KW - anthracyclines
KW - doxorubicin
KW - drug design
KW - multidrug resistance
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U2 - 10.1016/0163-7258(93)90007-Z
DO - 10.1016/0163-7258(93)90007-Z
M3 - Review article
C2 - 8022858
AN - SCOPUS:0027892892
SN - 0163-7258
VL - 60
SP - 215
EP - 234
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 2
ER -