Prodrug-Fludarabine

Creative Biolabs is a leading service provider that focuses on biomacromolecules engineering for research, diagnostic and therapeutic use. Based on advanced platforms and optimized strategies, we provide the best quality fludarabine as a prodrug for customers to develop a comprehensive antibody-directed enzyme prodrug therapy (ADEPT) development for targeted immunotherapy.

Fludarabine

Fludarabine is a chemotherapy medication, which is categorized into purine analog family of medications and works by disrupting the duplication of DNA. It was approved for medical use in the United States in 1991 and it was used to treat leukemia and lymphoma diseases including chronic lymphocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, and non-Hodgkin's lymphoma. As the most effective and safe medicines needed in a health system, it is on the World Health Organization's List of Essential Medicines. Combined with cytarabine and granulocyte colony-stimulating factor, it is also used in the treatment of acute myeloid leukemia. In addition, due to its immunosuppressive ability, it is also used in some conditioning regimens prior to allogeneic stem cell transplant.

Fludarabine chemical structure. Atoms are represented as spheres with conventional color coding. Fig.1 Fludarabine chemical structure. Atoms are represented as spheres with conventional color coding.

MOA of Fludarabine

The prodrug fludarabine can be activated by purine nucleoside phosphorylase hydrolysis, yielding the parent drug 2-fluoroadenine. 2-fluoroadenine is the nucleoside analogues which acts as pseudo-substrates in biochemical reactions. It could inhibit DNA replication by inhibiting enzymes involved in the de novo synthesis of nucleotides. In addition, the nucleoside analogues can be incorporated into DNA and RNA and thus interrupt the extension of DNA and RNA chains. At last, it inhibits enzymes which involved in the nucleic acid synthesis, such as DNA polymerase and nucleic acid reductase, thereby inhibiting DNA replication synthesis and repairs of nucleic acid macromolecules.

Fludarabine-based ADEPT

Compared with traditional cancer treatments, ADEPT serve to provide greater tumor specificity, potency, and reduce patient side effects. The fludarabine has been used as a prodrug in ADEPT. An antibody-PNP-AV fusion protein combined with an enzyme prodrug therapy has been used for the treatment of breast cancer. Cytotoxicity can be localized to the site of the tumor using a protein fusion of purine nucleoside phosphorylase (PNP) and annexin V. Annexin V has been treated as tumor-targeting component of the fusion protein as it could bind to phosphatidylserine expressed externally on cancer cells and the endothelial cells of the tumor vasculature, but not recognize the protein on normal vascular endothelial cells. PNP enzyme could convert the fludarabine into 2-fluoroadenine which is a more cytotoxic form.

Mechanism of ADEPT. Fig.2 Mechanism of ADEPT.

Creative Biolabs is committed to producing a safe and effective prodrug. Based on our tailored services and high-quality products, we are happy to help our clients develop fludarabine-based ADEPT.  We believe our advanced platform can greatly contribute to the success of your projects. Please feel free to contact us for more information.


For Research Use Only. NOT FOR CLINICAL USE.


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