Drug intelligence / Profile preview

volasertib + liposomal daunorubicin + fludarabine + cytarabine

Development stage
Unknown
Lead developer
Boehringer Ingelheim
Modality
Small Molecules, Liposomes → Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
Administration
Intravenous
01

Overview

This is a **combination regimen** consisting of four antineoplastic drugs: **volasertib**, **liposomal daunorubicin** (as CPX-351), **fludarabine**, and **cytarabine**, used experimentally for the treatment of acute myeloid leukemia (AML). Volasertib is a potent and selective inhibitor of Polo-like kinase 1 (PLK1), a critical regulator of cell division. Liposomal daunorubicin plus cytarabine (CPX-351, Vyxeos) is an approved fixed-ratio liposomal formulation that delivers daunorubicin, an anthracycline that intercalates DNA and inhibits topoisomerase II, and cytarabine, a nucleoside analog that inhibits DNA polymerase during the S-phase of cell division. Fludarabine is a purine analog that inhibits DNA synthesis by interfering with DNA polymerase and ribonucleotide reductase. This regimen aims to synergistically target leukemia cells via multiple mechanistic pathways: cell cycle inhibition (volasertib), DNA damage and replication stress (daunorubicin, cytarabine, fludarabine), and enhanced intracellular accumulation of cytotoxic nucleotides. The liposomal formulation enables maintenance of a pharmacodynamically synergistic ratio between daunorubicin and cytarabine for extended periods[1][2][3][5].

02

Targets

DNA polymerase familyRNR (Ribonucleotide reductase)PLK1 (Polo like kinase 1)PLK3TOP2A (DNA topoisomerase II)DNAPLK2 (Polo-like kinase 2)

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