Sandbox Reserved 390: Difference between revisions
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==ETOPOSIDE RESISTANCE== | ==ETOPOSIDE RESISTANCE== | ||
The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. This resistance occurs via two mechanisms: '''1)''' Decreased accumulation via increased [http://en.wikipedia.org/wiki/P-glycoprotein P-glycoprotein] ; and '''2)''' Changes in target proteins (mutation or decreased expression of topoisomerase II or decreased apoptosis due to mutation of | The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. This resistance occurs via two mechanisms: '''1)''' Decreased accumulation via increased [http://en.wikipedia.org/wiki/P-glycoprotein P-glycoprotein] ; and '''2)''' Changes in target proteins (mutation or decreased expression of topoisomerase II or decreased apoptosis due to mutation of [http://en.wikipedia.org/wiki/P53 P53]). | ||
'''1.''' Decreased accumulation via increased P-glycoprotein (a multidrug resistance): This drug resistance mechanism is characterized by decreased intracellular accumulation of drug facilitated by overexpression of the human multidrug resistance (mdrl) gene, causing overproduction of P-glycoprotein. This cell membrane protein acts as an export pump for a wide variety of unrelated foreign natural products. By maintaining lower intracellular levels of drug, lower drug concentration would be available to the target, which is topoisomerase II. | '''1.''' Decreased accumulation via increased P-glycoprotein (a multidrug resistance): This drug resistance mechanism is characterized by decreased intracellular accumulation of drug facilitated by overexpression of the human multidrug resistance (mdrl) gene, causing overproduction of P-glycoprotein. This cell membrane protein acts as an export pump for a wide variety of unrelated foreign natural products. By maintaining lower intracellular levels of drug, lower drug concentration would be available to the target, which is topoisomerase II. | ||