Prodrug-Doxorubicin-phenoxyacetamide

Creative Biolabs now provides high-quality doxorubicin-phenoxyacetamide as a prodrug for antibody-penicillin amidase conjugate-based ADEPT development. With the help of our advanced techniques and experienced scientists, we have confidence in delivering the most satisfactory products to facilitate diverse research projects.

Doxorubicin-phenoxyacetamide

Doxorubicin-phenoxyacetamide is a derivative of doxorubicin. It has been designed as a prodrug which can be activated in a site-specific manner by monoclonal antibody-penicillin amidase conjugates. It is less cytotoxic against adenocarcinoma cells than doxorubicin. Doxorubicin is a chemotherapy medication used to treat cancer including breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is generally used together with other chemotherapy agents. Doxorubicin was approved for medical use in 1974. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.

Fig.1 The chemical structure of doxorubicin.

MOA of Doxorubicin-phenoxyacetamide

Doxorubicin-phenoxyacetamide can be activated by penicillin amidase enzyme hydrolysis and thus yield the parent drug Doxorubicin. Doxorubicin is a potent DNA crosslinking agent that could interact with DNA by intercalation and inhibition of macromolecular biosynthesis. It can inhibit the migration of topoisomerase II which plays a crucial role in DNA transcription. Doxorubicin can stabilize the topoisomerase II complex during the DNA chain replication preventing the DNA double helix from being resealed and thereby stopping the process of replication. As a consequence, DNA damage response, epigenome, and transcriptome are deregulated in doxorubicin-exposed cells.

Fig.2 Best conformations for doxorubicin docked to DNA and tRNA (PDB entry 6TNA). The drug is shown in green color. (Agudelo, 2016)

Doxorubicin-phenoxyacetamide-based ADEPT

Antibody-directed enzyme prodrug therapy (ADEPT), which is aimed at increasing the selectivity and effectiveness of anti-cancer agents, is a promising approach for cancer chemotherapy. The N-phenylacetamido derivatives of doxorubicin were designed as prodrugs which could be activated in a site-specific manner by monoclonal antibody-penicillin-G amidase (mAb-PGA) conjugates. N-(Phenylacetamido) doxorubicin was found to be 10-fold less cytotoxic against H2981 lung adenocarcinoma cells than doxorubicin. When incubated with PGA, its cytotoxicity increased rapidly and became equivalent to that of the corresponding drugs from which they were made. In vitro cytotoxicity assays demonstrated that prodrug was at least 1000-fold less toxic than doxorubicin against H2981 cells (L6-antigen positive). The activation of doxorubicin-phenoxyacetamide on H2981 cells by L6-PGA occurred in an immunologically specific manner. These results demonstrate that doxorubicin-phenoxyacetamide prodrugs can be specifically activated by a mAb-PGA conjugate to release clinically approved anticancer agents in the ADEPT system. With abundant experience in drug development, Creative Biolabs is dedicated to offering stable quality prodrug-doxorubicin-phenoxyacetamide for antibody-penicillin amidase conjugate-based ADEPT development. We are always pleased to offer the best service and products to satisfy each demand from our global clients. Please contact us for more information and a detailed quote.

Reference

1. Agudelo, D.; et.al. Review on the binding of anticancer drug doxorubicin with dna and trna: structural models and antitumor activity. Journal of Photochemistry & Photobiology B Biology. 2016, 158, 274-279.

For Research Use Only. NOT FOR CLINICAL USE.