Berubicin: Anthracyclines inhibit the topoisomerase II enzyme to disrupt DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, thus preventing the replication of rapidly growing cancer cells.

Furthermore, anthracyclines inhibit the topoisomerase II enzyme, preventing relaxation of supercoiled DNA, thus blocking DNA transcription and replication. However, all previously studied anthracyclines are hampered due to their inability to cross the blood-brain-barrier, limiting their effectiveness to treat tumors in the brain.

One of the most important mechanisms of maintaining the blood-brain barrier are the multidrug resistance proteins that result in drug efflux.  Berubicin was designed from the conserved doxorubicin molecular structure and is tailor-made to improve lipophilicity by the addition of a 4’-O-benzyl substituent covalently bound to the anthracycline glycone ring. Its ability to circumvent ATP-binding cassette transporters, Multidrug Resistant Protein-1 (MRP1), P-glycoprotein (P-gp), and to penetrate the blood-brain barrier differentiates it from other clinically available anthracyclines.