Daunorubicin (DB00694): A Comprehensive Monograph on its Chemistry, Pharmacology, and Clinical Utility

Part I: Executive Summary

Daunorubicin is a foundational antineoplastic agent belonging to the anthracycline class of antibiotics. First isolated from Streptomyces species and approved for medical use in 1979, it has remained a cornerstone of chemotherapy for hematologic malignancies, particularly acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).[1] Its potent cytotoxic activity stems from a multifaceted mechanism of action, primarily involving the intercalation into DNA and the inhibition of topoisomerase II, an enzyme critical for DNA replication and repair. This dual action leads to catastrophic DNA damage and subsequent cancer cell apoptosis.[1]

However, the very mechanism that confers its efficacy is also responsible for its significant and often dose-limiting toxicities. The clinical use of daunorubicin is perpetually constrained by severe myelosuppression and a cumulative, dose-dependent cardiotoxicity that can manifest as potentially fatal congestive heart failure, sometimes months or even years after treatment completion.[3] This therapeutic paradox—where efficacy and toxicity are inextricably linked—has driven decades of clinical and pharmaceutical research aimed at optimizing its therapeutic index.