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cyclophosphamide + fludarabine + hydroxyurea + thiotepa

Development stage
Preclinical
Lead developer
Takeda
Modality
Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
Administration
Oral, Intravenous
01

Overview

This is a combination chemotherapy regimen consisting of four agents—cyclophosphamide, fludarabine, hydroxyurea, and thiotepa. Each drug has a distinct mechanism of action targeting rapidly dividing cells and is used primarily in the treatment of hematologic malignancies or as part of conditioning regimens for stem cell transplantation. Cyclophosphamide is an alkylating agent that crosslinks DNA, leading to cell death. Fludarabine is a purine analog that inhibits DNA synthesis by interfering with DNA polymerase and ribonucleotide reductase. Hydroxyurea inhibits ribonucleotide reductase, blocking the conversion of ribonucleotides to deoxyribonucleotides and thus inhibiting DNA synthesis[10]. Thiotepa is another alkylating agent that also crosslinks DNA strands. The combination aims to maximize cytotoxicity against malignant cells through multiple mechanisms affecting nucleic acid metabolism and repair.

02

Targets

DNA polymerase familyDNARNR (Ribonucleotide reductase)

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