amrubicinol

Amrubicinol is the primary active metabolite of **amrubicin**, a synthetic 9-aminoanthracycline antineoplastic agent. It is formed in vivo through the reduction of the C-13 ketone group of amrubicin, a reaction mediated by carbonyl reductase. Amrubicinol is significantly more potent than its parent compound—estimated to be 5 to 54 times more active—and is the principal mediator of the drug's therapeutic and toxic effects. Its mechanism of action involves the inhibition of **DNA topoisomerase II**, where it stabilizes the enzyme-DNA cleavable complex, leading to double-strand DNA breaks and apoptosis. Clinically, amrubicinol levels are closely monitored in pharmacokinetic studies of amrubicin, particularly in the treatment of **small cell lung cancer (SCLC)** and **non-small cell lung cancer (NSCLC)**, as its systemic exposure (AUC) is a major predictor of hematological toxicities such as grade 4 neutropenia. Resistance to amrubicinol has been associated with the overexpression of the MDR1 gene (P-glycoprotein) and the growth factor amphiregulin.

Other names

13-hydroxyamrubicinamrubicin-OH