Prodrug-Doxorubicin Phosphate

Creative Biolabs now provides high-quality doxorubicin phosphate as a prodrug for antibody-directed enzyme prodrug therapy (ADEPT) development. With the help of advanced techniques and experienced scientific staffs, we have confidence in delivering the most satisfactory products and services to facilitate diverse research projects.

Doxorubicin Phosphate

Doxorubicin phosphate is a prodrug compound synthesized from doxorubicin and phosphate. The parent drug is doxorubicin which is a chemotherapy medication used to treat cancer including breast cancer, Kaposi's sarcoma, bladder cancer, lymphoma, and acute lymphocytic leukemia. It is often used combined with other chemotherapy agents to achieve a more potent efficacy. Doxorubicin was approved for medical use in the United States in 1974 because of its potency in cancer treatment. It is on the World Health Organization's List of Essential Medicines. Particularly, it has been treated as the most effective and safe medicines needed in a health system.

The chemical structure of Doxorubicin. Fig.1 The chemical structure of Doxorubicin.

MOA of Doxorubicin Phosphate

Doxorubicin is the parent drug of doxorubicin phosphate, which is a chemotherapy medication used to treat cancer. It is a potent DNA crosslinking agent interacting with DNA by intercalation and inhibition of macromolecular biosynthesis. It inhibits the moving of topoisomerase II, an enzyme which relaxes supercoils during DNA transcription. Doxorubicin can stabilize the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. In addition, after intercalation, doxorubicin can also trigger histone extrusion from transcriptionally active chromatin. As a result, DNA damage response, epigenome, and transcriptome are deregulated in doxorubicin-exposed cells.

Structure of the doxorubicin-DNA complex. Doxorubicin intercalates into DNA and pushes apart the flanking base pairs with the sugar moiety sitting in the minor groove. Fig 2. Structure of the doxorubicin-DNA complex. Doxorubicin intercalates into DNA and pushes apart the flanking base pairs with the sugar moiety sitting in the minor groove. (Fan, 2014)

Doxorubicin Phosphate-based ADEPT

The use of doxorubicin phosphate as a prodrug in ADEPT development is under active development and evaluation. In the ADEPT, the specific monoclonal antibody harbors the targeted capability to deliver unique functional enzymes exclusively to the tumor site, thereby reducing the damage to normal tissues. Research showed that scFv mAb bound to tumor antigen, with the nontoxic prodrug activated by the enzyme to the toxic drug (Doxorubicin) at the tumor site. The cytotoxicity is comparable to the free drug. The active drug can diffuse to nearby cells, leading to a local bystander effect where antigen-negative cells and tumor supportive stromal elements are destroyed to kill tumor cells effectively.

Creative Biolabs now offers reliable quality doxorubicin phosphate as a prodrug for antibody-alkaline phosphatase conjugate-based ADEPT development. Our scientists will work closely with you to keep you apprised of project progress while taking all your goals into account. We also provide various customized ADEPT products and services. Please feel free to contact us for a detailed quote.

Reference

  1. Fan, Y.; et al. Doxorubicin, dna torsion, and chromatin dynamics. Biochimica Et Biophysica Acta. 2014, 1845(1), 84-89.

Related Sections

Antibody-directed Enzyme Prodrug Therapy (ADEPT): Antibody-enzyme Conjugates for Cancer Therapy: Services:
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