Prodrug-Daunorubicin Glucuronide

Creative Biolabs is a leader in the field of antibody-drug conjugates (ADCs) development. We are pleased to offer daunorubicin glucuronide as a prodrug for customized antibody-directed enzyme prodrug therapy (ADEPT) development services. Your trust is our powerful motivation to meet your demands.

Daunorubicin Glucuronide

Daunorubicin glucuronide is a type of prodrug synthesized from daunorubicin and glucuronide. A glucuronide, which is also referred to as glucuronoside, is substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. The prodrug can be catalyzed producing the parent drug daunorubicin, which is one of the anthracyclines chemotherapy medication with potent antitumor agents that have been widely used in the clinic for the treatment of numerous malignancies such as leukemias, lymphomas, soft-tissues sarcomas, breast, uterine and ovarian cancers.

Fig.1 Glucuronide prodrugs of doxorubicin and daunorubicin. (Tranoy-Opalinski, 2014)

MOA of Daunorubicin Glucuronide

The β-glucuronidase enzyme catalyzes the cleavage of prodrug daunorubicin glucuronide to yield effective daunorubicin, which is a chemotherapy medication used to treat cancer. Daunorubicin is a potent DNA crosslinking agent which interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. It inhibits the move of topoisomerase II, an enzyme which relaxes supercoils during DNA transcription. Daunorubicin 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.

Daunorubicin Glucuronide-based ADEPT

In this daunorubicin glucuronide-based ADEPT, daunorubicin glucuronide is a potential prodrug can be activated by an effective enzyme. Suitable monoclonal antibodies can be employed to specifically target tumor cell antigen to promote the treatment of cancer in ADEPT. For example, the CD20 antigen, which can be recognized by the anti-CD20 antibody, is an attractive target for the specific treatment of B-cell lymphoma.  A fusion protein of the single-chain Fv anti-CD20 mouse monoclonal antibody (MoAb) 1H4 and human β-glucuronidase can effectively activate the nontoxic prodrug N-[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-β-glucuronyl carbamate to produce doxorubicin at the tumor site. The nontoxic prodrug is a type of daunorubicin glucuronide prodrug can be hydrolyzed by the fusion protein at a hydrolysis rate similar to that of human β-glucuronidase. When the fusion protein specifically binds to Daudi lymphoma cells, the prodrug produces similar antiproliferative effects as doxorubicin. Therefore, it is feasible to construct a eukaryotic fusion protein consisting of an anti-CD20 antibody and human β-glucuronidase for future use in the activation of anticancer prodrugs in B-cell lymphoma.

Fig.2 General action mode of prodrugs containing a self-immolative spacer. (Tranoy-Opalinski, 2014)

Equipped with advanced organic synthesis platform and experienced scientists, Creative Biolabs is dedicated to offering high-quality prodrug such as the daunorubicin glucuronide for antibody-purine nucleoside phosphorylase conjugate-based ADEPT development service in a timely and cost-effective manner. Our customarily tailored services and high-quality products will contribute greatly to the success of your projects. Any question about ADEPT development, please contact us for more information and a detailed quote.

Reference

1. Tranoy-Opalinski, I.; et al. β-Glucuronidase-responsive prodrugs for selective cancer chemotherapy: an update. European journal of medicinal chemistry. 2014, 74, 302-313.

For Research Use Only. NOT FOR CLINICAL USE.