Dexrazoxane Hydrochloride

Dexrazoxane is a bisdioxopiperazine compound developed to reduce anthracycline cardiotoxicity without compromising antitumor efficacy. It acts through two primary mechanisms: hydrolysis to its active ring-opened metabolite ADR-925, which chelates iron and prevents iron-dependent oxidative stress in cardiac tissue, and inhibition of topoisomerase II catalytic activity. Preclinical studies in six animal species confirmed that dexrazoxane reduces doxorubicin-induced cardiac injury and also mitigates the toxicity of anthracycline extravasation. The review details the biochemistry, metabolism, and pharmacokinetics of dexrazoxane, highlighting its utility as a cardioprotectant and as an antidote for accidental anthracycline extravasation.

Fig. 1 The X-ray structure of the binding of dexrazoxane to the N-terminal ATP binding region of the yeast topoisomerase IIα dimer. (Herman E H.; et al. 2014)