Prodrug-CPT-11

Creative Biolabs is dedicated to offering a full package of antibody-directed enzyme prodrug therapy (ADEPT) development services. At present, we can provide high-quality CPT-11 (Irinotecan) as an effective and safe prodrug for antibody-carboxylesterases conjugate-based ADEPT development.

CPT-11

CPT-11 (Irinotecan) is a medication used to treat colon cancer, and small cell lung cancer. It is used either alone or with fluorouracil for colon cancer treatment. Irinotecan was approved for medical use in 1996. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Irinotecan can be activated by hydrolysis to SN-38, an inhibitor of topoisomerase I.

Fig.1 Illustration of the CPT-11 (Irinotecan) pathway. (Yu, 2005)

MOA of CPT-11

CPT-11 (Irinotecan), which is catalytic hydrolysis by exclusively enzyme such as carboxylesterase, yielding parent drug SN38, can be used as a prodrug. The SN38 is a potent antineoplastic drug. It is a topoisomerase I inhibitor that can inhibit the replication of the DNA. It is the active metabolite of irinotecan but has 1000 times more activity than irinotecan itself. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold. Upon prodrug CPT-11 is administrated into the tumor site, the carboxylesterase can catalyze it to produce effective drug immediately to perform its cytotoxic effects.

Fig.2 Glucuronidation of SN-38 after esterase cleavage of irinotecan. The scheme depicts the lactone and carboxylate species of each compound. (Tallman, 2005)

CPT-11-based ADEPT

The use of CPT-11 as the prodrug in ADEPT is under active development and evaluation. An anti-p97 mAb 96.5 was linked to hCE-2, forming a conjugate that could bind to antigen-positive cancer cells and convert CPT-11 to SN-38. In vitro cytotoxicity detection was performed on 3677 melanoma cells (p97 antigen positive). Cells treated with the 96.5-hCE-2 and CPT-11 present sensitized to CPT-11. These results suggested that the enzyme within the conjugate is active and capable of activating CPT-11 under the conditions used in the cytotoxicity experiments.

Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs is always dedicated to assisting our clients with the most satisfactory ADEPT related services and products. Now we proudly offer customized CPT-11 as a prodrug for antibody-carboxylesterases conjugate-based ADEPT development. If you are interested in other ADEPT services, please contact us for more details.

References

1. Yu, J.; et al. Gene expression profiling of the irinotecan pathway in colorectal cancer. Clinical Cancer Research An Official Journal of the American Association for Cancer Research. 2005, 11(5), 2053.
2. Tallman, M. N.; et al. Differential rates of glucuronidation for 7-ethyl-10-hydroxy-camptothecin (sn-38) lactone and carboxylate in human and rat microsomes and recombinant udp-glucuronosyltransferase isoforms. Drug Metabolism & Disposition the Biological Fate of Chemicals.2005, 33(7), 977.

For Research Use Only. NOT FOR CLINICAL USE.