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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Inhibitors of Multidrug Resistance to Antitumor Agents (MDR)

Author(s): Carmen Avendano and J. Carlos Menendez

Volume 9 , Issue 2 , 2002

Page: [159 - 193] Pages: 35

DOI: 10.2174/0929867023371175

Price: $65

Abstract

Multidrug resistance is one of the main obstacles in the chemotherapy of cancer. Its inhibition by combination of chemosensitizers with antitumor compounds is a very active field of research, since safe and potent reversal agents would be beneficial for clinical use. Most modulators act by binding to membrane transport proteins (specially P-gp and MRP) and inhibiting their drug-effluxing activity, or by indirect mechanisms related to phosphorylation of the transport proteins or expression of the mdr1 and mrp1 genes. The main body of the review focuses on the study of the known MDR modulators, which are classified according to their chemical structures. General structure-activity studies of this therapeutic group are hampered by the very heterogeneous chemical structure of the compounds, although some conclusions have been drawn from the study of homogeneous series of molecules.

Keywords: Multidrug Resistance, Antitumor Agents, P-gp, topoisomerase II, Doxorubicin, Daunorub icin, Vincristine, Vinblastine, Colchicine, P acli ta xel


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