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A doxorubicin metabolite
Doxorubicinol is the major metabolite of doxorubicin , an anthracycline antitumor antibiotic that inhibits DNA topoisomerase II by inducing double-stranded DNA breaks. Doxorubicinol is formed by NADPH-dependent reduction of the side chain carbonyl group of doxorubicin in human, rabbit, and canine cardiac tissue. Doxorubicinol inhibits sodium-potassium-dependent ATPase activity (IC50 = 5.40 μg/ml) and ATP-dependent calcium uptake (IC50= 4.5 μg/ml) in canine cardiac muscle and increases resting stress in contracting rabbit cardiac muscle. Clinically observed cardiotoxicities following doxorubicin treatment have been attributed to the formation and cardiac action of doxorubicinol.
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