Drug intelligence / Profile preview

busulfan + cyclophosphamide + fludarabine

Development stage
Unknown
Lead developer
GSK
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules, DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a combination chemotherapy regimen consisting of three small molecule alkylating and antimetabolite agents—busulfan, cyclophosphamide, and fludarabine. It is primarily used as a conditioning protocol prior to allogeneic hematopoietic stem cell transplantation (HSCT), including haploidentical transplants. The combination works synergistically to ablate bone marrow and suppress the immune system in preparation for engraftment. Busulfan and cyclophosphamide are both alkylating agents that cause DNA crosslinking and cell death; fludarabine is a purine analog antimetabolite that inhibits DNA synthesis by interfering with DNA polymerase and ribonucleotide reductase activity. This regimen has been studied for use in various hematologic malignancies (such as acute myeloid leukemia) as well as non-malignant disorders like adrenoleukodystrophy or mucopolysaccharidoses[1][4].

Other names
busulfancyclophosphamidefludarabineBFC conditioning regimen
02

Targets

POLA1 (DNA polymerase alpha)RNR (Ribonucleotide reductase)DNA-directed primase/polymerase protein (PrimPol)DNALIG1 (DNA ligase 1)

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