Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9028118 | Chemico-Biological Interactions | 2005 | 5 Pages |
Abstract
The anticancer prodrug CPT-11 is a highly effective camptothecin analog that has been approved for the treatment of colon cancer. The 2.6Â Ã
resolution crystal structure of its complex with Torpedo californica acetylcholinesterase (TcAChE) demonstrates that CPT-11 binds to TcAChE and spans its gorge similarly to the Alzheimer drug, Aricept. The crystal structure clearly reveals the interactions, which contribute to the inhibitory action of CPT-11. Modeling of the complexes of CPT-11 with mammalian butyrylcholinesterase and carboxylesterase, both of which are known to hydrolyze the drug, shows how binding to either of the two enzymes yields a productive substrate-enzyme complex.
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Authors
Michal Harel, Janice L. Hyatt, Boris Brumshtein, Christopher L. Morton, Randy M. Wadkins, Israel Silman, Joel L. Sussman, Philip M. Potter,