Prodrug-Glycosides

Creative Biolabs has established advanced technology platforms for large scale drug production. Now, we offer effective and high-quality glycosides as a prodrug for antibody-glycosidases conjugate-based ADEPT in cancer treatment.

Glycosides

In chemistry, glycoside is a molecule which consists of a sugar combining with another functional group via a glycosidic bond. Glycosides play important roles in many processes of living organisms. In plants, some chemicals are stored in an inactive glycosides form.

After hydrolysis by an enzyme which leads to the sugar part to be cleaved, the chemical is available for use. In addition, many glycosides are used as medications. In animals and humans, poisons are often bound to sugar molecules as part of their elimination from the body. Glycosides can be used as a prodrug in ADEPT to produce a potent antitumour antibiotics duocarmycins. The duocarmycins alkylating agents can bind to the minor groove of DNA and alkylate the nucleobase adenine at the N3 position, causing the tumor cell death. The duocarmycins are suitable to target solid tumors.

Fig.1 The chemical structure of glycosides.

MOA of Glycosides

Glycosidases enzyme catalyzes the hydrolysis of prodrug glycosides, yielding parent drug duocarmycins. Duocarmycins are a kind of alkylating agents that can bind to the minor groove of DNA and alkylate the nucleobase adenine at the N3 position. The irreversible alkylation of DNA disrupts the nucleic acid architecture, which finally leads to tumor cell death. The duocarmycin analogues are able to exert their mode of action at any phase in the cellular cycle, whereas tubulin binders will only attack tumor cells when they are in a mitotic state. Abundant evidence suggests that DNA damaging agents, such as duocarmycins, are more potent in tumor cell killing than tubulin binders, particularly in the case of solid tumors.

Fig.2 Molecular model of distamycin (shown in red) in the minor groove of DNA. (Khan, 2012)

Glycosides-based ADEPT

In ADEPT system, the use of glycosides as the prodrug is under active evaluation. Glycosides are prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. The previous study demonstrated that the prodrug presented very low toxicity when cultured with carcinoma cells of line A549. However, in the ADEPT strategy based on the glycosidases, after addition of the corresponding enzymes and exposure for 24 h at prodrug concentrations of <0.1 mM, the proliferation of the carcinoma cells was inhibited almost completely. The ability of this easily administered ADEPT system to produce significant effects on tumor cells proliferation suggests that this is a promising therapy method.

Creative Biolabs is committed to assisting our clients with the most satisfactory ADEPT products and related services. Now we provide reliable quality glycosides as a prodrug for antibody-glycosidases conjugate-based ADEPT development. If you are interested in other various ADEPT services and products, please feel free to contact us for more details.

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