Sandbox Reserved 390: Difference between revisions

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OCA, Arthur Cox, Eyitayo Akoda

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 ==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 P-glycoprotein; and '''2)''' Changes in target proteins (mutation or decreased expression of topoisomerase II or decreased apoptosis due to mutation of p53).
+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 p53).
-'''1.'''	Decreased accumulation via increased [http://en.wikipedia.org/wiki/P-glycoprotein 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.
 '''2.'''	Changes in target proteins: This mechanism relates directly to the target enzyme; Either low enzyme levels or altered sensitivity of the enzyme for the drug confers resistance to that drug. This mechanism also confers a form of multidrug resistance; in that resistance to one topoisomerase II inhibitor through decreased or altered topoisomerase activity generally translates into resistance to most other topoisomerase II inhibitors.