Design and tumor targeting of anthracyclines able to overcome multidrug resistance: A double-advantage approach

Waldemar Priebe, Roman Perez-Soler

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)215-234
Number of pages20
JournalPharmacology and Therapeutics
Volume60
Issue number2
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Anthracyclines
Multiple Drug Resistance
Doxorubicin
Neoplasms
Drug Design
P-Glycoprotein
Drug Delivery Systems
Liposomes
Drug Therapy
Pharmaceutical Preparations

Keywords

  • anamycin
  • anthracyclines
  • Antitumor agents
  • doxorubicin
  • drug design
  • multidrug resistance

ASJC Scopus subject areas

  • Pharmacology

Cite this

Design and tumor targeting of anthracyclines able to overcome multidrug resistance : A double-advantage approach. / Priebe, Waldemar; Perez-Soler, Roman.

In: Pharmacology and Therapeutics, Vol. 60, No. 2, 1993, p. 215-234.

Research output: Contribution to journalArticle

@article{2e4947fd3f354b5f877472cca6771f8b,
title = "Design and tumor targeting of anthracyclines able to overcome multidrug resistance: A double-advantage approach",
abstract = "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.",
keywords = "anamycin, anthracyclines, Antitumor agents, doxorubicin, drug design, multidrug resistance",
author = "Waldemar Priebe and Roman Perez-Soler",
year = "1993",
doi = "10.1016/0163-7258(93)90007-Z",
language = "English (US)",
volume = "60",
pages = "215--234",
journal = "Pharmacology and Therapeutics",
issn = "0163-7258",
publisher = "Elsevier Inc.",
number = "2",

}

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 - anamycin

KW - anthracyclines

KW - Antitumor agents

KW - doxorubicin

KW - drug design

KW - multidrug resistance

UR - http://www.scopus.com/inward/record.url?scp=0027892892&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027892892&partnerID=8YFLogxK

U2 - 10.1016/0163-7258(93)90007-Z

DO - 10.1016/0163-7258(93)90007-Z

M3 - Article

C2 - 8022858

AN - SCOPUS:0027892892

VL - 60

SP - 215

EP - 234

JO - Pharmacology and Therapeutics

JF - Pharmacology and Therapeutics

SN - 0163-7258

IS - 2

ER -