4-ISOXAZOLYL-1,4-DIHYDROPYRIRINES BIND THE MULTIDRUG-RESISTANCE TRANSPORTER
type: CreativeWork
description: The development of multidrug resistance in tumor cells has been recognized as a major obstacle to successful cancer treatment. Tumor cells in vitro and in vivo can develop multidrug resistance (MDR) to the lethal effects of a variety of cytotoxic drugs used to treat cancerous tumor cells. The over expression of multiple drug resistance gene 1 has been correlated with the expression of multi drug resistance protein 1(MDR1, also known as P-glycoprotein or P-gp). MDR1's role in altering uptake, distribution and bioavailability is considered a significant factor when examining drugs for clinical administration, and represents a viable drug target for the reversal of MDR. MDR1 is driven by ATP hydrolysis and as such it shares both sequence and structural homology with proteins that are energy-dependent efflux transporters driven by ATP hydrolysis, making MDR1 a member of the ATP binding cassette (ABC) super family. Because, MDR1 transports substrates that are often toxic xenobiotics, MDR1 is thought to fulfill a cellular detoxification function. As such it is expressed in several tissues in the body such as the liver, pancreas, kidney, colon, intestinal mucosa, and in the blood brain barrier. Due to its presences in a wide variety of cells it has been suggested that MDR1 is involved in protection of the organism as a whole. Consequently, the overproduction of MDR1 is seen in cancer cells. MDR1 has been shown to transport a wide variety of lipophilic agents, of importance, MDR1 effluxes chemotherapeutics agents out of the cell resulting in a low and ineffective intracellular drug concentration. Thus, the over production of MDR1 in cancer cells can then be thought of as a protective factor for cancer cells, and as an effect causes MDR cancer cells. Therefore, understanding MDR1â€™s function is important for controlling the bioavailability of drugs and for improving anticancer chemotherapy. Reversal of multidrug resistance is of interest, and MDR reversing agents have been …
abstract: The development of multidrug resistance in tumor cells has been recognized as a major obstacle to successful cancer treatment. Tumor cells in vitro and in vivo can develop multidrug resistance (MDR) to the lethal effects of a variety of cytotoxic drugs used to treat cancerous tumor cells. The over expression of multiple drug resistance gene 1 has been correlated with the expression of multi drug resistance protein 1(MDR1, also known as P-glycoprotein or P-gp). MDR1's role in altering uptake, distribution and bioavailability is considered a significant factor when examining drugs for clinical administration, and represents a viable drug target for the reversal of MDR. MDR1 is driven by ATP hydrolysis and as such it shares both sequence and structural homology with proteins that are energy-dependent efflux transporters driven by ATP hydrolysis, making MDR1 a member of the ATP binding cassette (ABC) super family. Because, MDR1 transports substrates that are often toxic xenobiotics, MDR1 is thought to fulfill a cellular detoxification function. As such it is expressed in several tissues in the body such as the liver, pancreas, kidney, colon, intestinal mucosa, and in the blood brain barrier. Due to its presences in a wide variety of cells it has been suggested that MDR1 is involved in protection of the organism as a whole. Consequently, the overproduction of MDR1 is seen in cancer cells. MDR1 has been shown to transport a wide variety of lipophilic agents, of importance, MDR1 effluxes chemotherapeutics agents out of the cell resulting in a low and ineffective intracellular drug concentration. Thus, the over production of MDR1 in cancer cells can then be thought of as a protective factor for cancer cells, and as an effect causes MDR cancer cells. Therefore, understanding MDR1â€™s function is important for controlling the bioavailability of drugs and for improving anticancer chemotherapy. Reversal of multidrug resistance is of interest, and MDR reversing agents have been …
author: Steiger, Scott
keywords: Dihydropyrirines, Isoxazolyl, MDR1, Multidrug-Resistance Transporter, P-gp
date published: 2013-01-01T08:00:00Z
date modified: 2026-07-24T03:10:20Z
provider: University of Montana
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Montana