Drug intelligence / Profile preview

cladribine + cytarabine + pegylated liposomal doxorubicin

Development stage
Preclinical
Lead developer
Johnson & Johnson
Modality
Small Molecules, Liposomes → Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
Administration
Intravenous, Subcutaneous
01

Overview

This is a combination chemotherapy regimen consisting of three agents: - **Cladribine** is a purine antimetabolite that interferes with DNA synthesis, leading to apoptosis in lymphocytes. It is primarily used for hematological malignancies such as hairy cell leukemia and has also been studied in acute myeloid leukemia (AML)[3][4]. - **Cytarabine** is a pyrimidine nucleoside analog that inhibits DNA polymerase, thereby blocking DNA synthesis and repair. It is widely used in the treatment of AML and other leukemias[2][5]. - **Pegylated liposomal doxorubicin** is an anthracycline antibiotic encapsulated in liposomes with polyethylene glycol (PEG), which enhances its circulation time and reduces cardiotoxicity compared to conventional doxorubicin. Doxorubicin intercalates into DNA, inhibiting topoisomerase II and generating free radicals that damage cellular components. This specific triple-drug combination does not have an established brand or regimen name but represents an investigational or off-label approach for treating hematologic malignancies such as AML or high-risk myelodysplastic syndromes (MDS). While combinations of cladribine plus cytarabine are documented for AML/MDS after azacitidine failure[4], the addition of pegylated liposomal doxorubicin would be expected to further enhance antileukemic activity by adding another mechanism targeting rapidly dividing cells.

02

Targets

DNA polymerase familyPol III (Dna-directed RNA polymerase III)TOP2A (DNA topoisomerase II)DNAPNP (Purine nucleoside phosphorylase)RNR (Ribonucleotide reductase)

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