Drug intelligence / Profile preview

melphalan + etoposide + cytarabine + amsacrine

Development stage
Preclinical
Lead developer
GSK
Modality
Small Molecules
Administration
Intravenous
01

Overview

This is a combination chemotherapy regimen consisting of four small-molecule antineoplastic agents: melphalan, etoposide, cytarabine, and amsacrine. Each component has a distinct mechanism of action targeting DNA synthesis or function: - **Melphalan** is an alkylating agent that crosslinks DNA strands, inhibiting DNA and RNA synthesis. - **Etoposide** inhibits topoisomerase II, leading to double-strand breaks in DNA and subsequent cell death. - **Cytarabine** is a nucleoside analog that interferes with DNA polymerase during the S-phase of the cell cycle, inhibiting DNA synthesis. - **Amsacrine** intercalates into DNA and inhibits topoisomerase II activity. This combination is used as high-dose chemotherapy for conditioning prior to autologous stem cell transplantation or bone marrow transplantation in hematologic malignancies such as lymphoma (including Hodgkin's disease), leukemia, and other cancers. The rationale for combining these agents is their complementary mechanisms of action against rapidly dividing malignant cells.

02

Targets

DNADNA polymerase familyTOP2A (DNA topoisomerase II)

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