Prodrug-5-fluorocytosine

Creative Biolabs has gained abundant experience in antibody-directed enzyme prodrug therapy (ADEPT) development. Prodrug plays a critical role in ADEPT development, now we offer reliable quality prodrug-5-fluorocytosine for antibody-β-lactamase conjugate-based ADEPT development. Our optimized conjugation strategies and advanced technology platforms will greatly contribute to your research and projects.

5-fluorocytosine

5-fluorocytosine (5-FC), also known as flucytosine, was first made in 1957. It is an antifungal medication which belongs to fluorinated pyrimidine analogue family. It can be converted into fluorouracil inside fungus to inhibit the synthesization of protein in fungus. In detail, flucytosine is intrafungally converted into cytostatic fluorouracil, which will be activated and yield the 5-fluorouridinetri phosphate further to disturb the producing of certain essential proteins of fungus by interacting with RNA biosynthesis. Besides, the 5-fluorocytosine can also transform into 5-fluorodeoxyuridine monophosphate to inhibit fungal DNA synthesis.

Schematic diagram of the effect of 5-fluorocytosine on the fungal cell. Fig.1 Schematic diagram of the effect of 5-fluorocytosine on the fungal cell. (Kabir, 2013)

MOA of 5-fluorocytosine

The 5-fluorocytosine prodrug can be catalyzed by the cytosine deaminase and thus yield high cytotoxic drug 5-fluorouracil. 5-fluorouracil has been used as a thymidylate synthase (TS) inhibitor to treat cancer. It blocks the synthesis of the pyrimidine thymidine by interrupting the action of thymidylate synthase. However, the pyrimidine thymidine is a critical nucleoside material required for DNA replication. Thymidylate synthase methylates deoxyuridine monophosphate (dUMP) to synthesize thymidine monophosphate (dTMP). Administration of 5-fluorouracil leads to a scarcity of dTMP and dividing cancerous cells undergo cell death via thymineless death. Calcium folinate offers an exogenous source of reduced folinates to stabilize the 5-FU-TS complex, thus promote 5-FU's cytotoxicity.

FU metabolism and the role of Smug1. FU is converted to the active precursors FUTP, FdUTP, and FdUMP (boldface); these can be incorporated into RNA, DNA, or inhibit TS, respectively. Fig.2 FU metabolism and the role of Smug1. FU is converted to the active precursors FUTP, FdUTP, and FdUMP (boldface); these can be incorporated into RNA, DNA, or inhibit TS, respectively. (An, 2007)

5-fluorocytosine-based ADEPT

5-fluorocytosine combining with cytosine deaminase (CD) has been used as a prodrug in ADEPT. CD is a microbial enzyme found in bacteria and yeast that can convert the antifungal agent 5-FC into the antitumor agent, 5-fluorouracil (5-FU). The enzyme was linked to the L6 monoclonal antibody, forming a conjugate that recognized antigens on the H2981 lung adenocarcinoma. Results showed that there were very high tumor/blood ratios of L6-CD (42/1) in vivo. Besides, significantly more 5-FC could be administered than 5-FU. L6-CD converted 5-FC into 5-FU resulted in 17 times more intratumoral 5-FU when compared to systemic 5-FU administration. Importantly, the conversion of 5-FC into 5-FU was low in blood, kidneys, and liver. This indicated that a major increase in intratumoral drug concentrations can be attained with a monoclonal antibody-enzyme conjugate in combination with an anticancer prodrug compared to systemic drug therapy.

The experienced scientists at Creative Biolabs are committed to providing high-quality 5-fluorocytosine as a prodrug to help you develop ADEPT in a cost-effective manner. Our perfect and tailored services will contribute greatly to the success of your projects. If you need some other services regarding ADEPT development, please contact us for more information and a detailed quote.

References

  1. Kabir, M. A.; Ahmad, Z. Candida infections and their prevention. Isrn Prev Med. 2013, 2013(5), 763628-763628.
  2. An, Q.; et al. 5-fluorouracil incorporated into dna is excised by the smug1 dna glycosylase to reduce drug cytotoxicity. Cancer Research. 2007, 67(3), 940.

For Research Use Only. NOT FOR CLINICAL USE.


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