TY - JOUR
T1 - Preclinical evaluation of new anthracyclines
AU - Garnier-Suillerot, Ariette
AU - Marbeuf-Gueye, Carole
AU - Salerno, Milena
AU - Loetchutinat, Chatchanok
AU - Fokt, Izabela
AU - Krawczyk, Marta
AU - Kowalczyk, Teresa
AU - Priebe, Waldemar
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - We designed a screening system for new anthracyclines totally based on human tumor material. In the first step of the system, the relative cytotoxicity versus doxorubicin of all new compounds is investigated in a panel of human tumor cell lines, well characterized for resistance factors and p53 status. Only a few analogs are selected through this step for further evaluation. The second step is aimed to investigate the therapeutic efficacy and the tolerability of the analog, which is compared to doxorubicin in a series of human tumor xenografts selected for presenting natural or acquired (by known mechanisms) resistance to the parent drug. Cardiotoxicity in mice is also studied. Cellular and molecular pharmacology studies are also considered. The results of a series of disaccharide anthracycline analogs screened by the system are presented. An analog of the series, MEN 10755, was selected for clinical investigation and is currently evaluated in Phase I trials. The ability of human tumor xenografts to predict the clinical efficacy of anthracycline analogs is also discussed.
AB - We designed a screening system for new anthracyclines totally based on human tumor material. In the first step of the system, the relative cytotoxicity versus doxorubicin of all new compounds is investigated in a panel of human tumor cell lines, well characterized for resistance factors and p53 status. Only a few analogs are selected through this step for further evaluation. The second step is aimed to investigate the therapeutic efficacy and the tolerability of the analog, which is compared to doxorubicin in a series of human tumor xenografts selected for presenting natural or acquired (by known mechanisms) resistance to the parent drug. Cardiotoxicity in mice is also studied. Cellular and molecular pharmacology studies are also considered. The results of a series of disaccharide anthracycline analogs screened by the system are presented. An analog of the series, MEN 10755, was selected for clinical investigation and is currently evaluated in Phase I trials. The ability of human tumor xenografts to predict the clinical efficacy of anthracycline analogs is also discussed.
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U2 - 10.2174/0929867013373949
DO - 10.2174/0929867013373949
M3 - Article
C2 - 11172688
AN - SCOPUS:0035041655
SN - 0929-8673
VL - 8
SP - 9
EP - 13
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 1
ER -