Old drug new use - Amoxapine and its metabolites as potent bacterial 1 β - glucuronidase inhibitors for alleviating cancer drug toxicity
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چکیده
*To whom correspondence should be addressed: 18 Hong Zhao 19 Department of Systems Medicine and Bioengineering 20 Houston Methodist Research Institute, Weill Cornell Medical College 21 6670 Bertner Ave., R6-216, Houston, TX 77030 22 E-mail: [email protected] 23 Phone: 713-441-3557; Fax: 713-441-7189 24 John E. Scott 25 Biomanufacturing Research Institute and Technology Enterprise 26 North Carolina Central University 27 1801 Fayetteville St., BRITE Bldg., Rm. 1019, Durham, NC 27707 28 Email: [email protected] 29 Phone: 919-530-7569 30
منابع مشابه
Old drug new use--amoxapine and its metabolites as potent bacterial β-glucuronidase inhibitors for alleviating cancer drug toxicity.
PURPOSE Irinotecan (CPT-11) induced diarrhea occurs frequently in patients with cancer and limits its usage. Bacteria β-glucuronidase (GUS) enzymes in intestines convert the nontoxic metabolite of CPT-11, SN-38G, to toxic SN-38, and finally lead to damage of intestinal epithelial cells and diarrhea. We previously reported amoxapine as a potent GUS inhibitor in vitro. To further understand the m...
متن کاملMolecular insights into microbial β-glucuronidase inhibition to abrogate CPT-11 toxicity.
Bacterial β-glucuronidases expressed by the symbiotic intestinal microbiota appear to play important roles in drug-induced epithelial cell toxicity in the gastrointestinal (GI) tract. For the anticancer drug CPT-11 (irinotecan) and the nonsteroidal anti-inflammatory drug diclofenac, it has been shown that removal of the glucuronide moieties from drug metabolites by bacterial β-glucuronidases in...
متن کاملStructure and Inhibition of Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity.
The selective inhibition of bacterial β-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative β-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, an...
متن کاملMolecular Insights into Microbial b-Glucuronidase Inhibition to Abrogate CPT-11 Toxicity
Bacterial b-glucuronidases expressed by the symbiotic intestinal microbiota appear to play important roles in druginduced epithelial cell toxicity in the gastrointestinal (GI) tract. For the anticancer drug CPT-11 (irinotecan) and the nonsteroidal anti-inflammatory drug diclofenac, it has been shown that removal of the glucuronide moieties from drug metabolites by bacterial b-glucuronidases in ...
متن کاملA High Throughput Assay for Discovery of Bacterial β-Glucuronidase Inhibitors
CPT-11 is a widely-used anti-cancer drug that is converted in vivo to its active metabolite, SN-38. In the liver, enzymes detoxify SN-38 by coupling it to a glucuronidate moiety and this inactive compound (SN-38G) is excreted into the gastrointestinal tract. In the intestine, commensal bacteria convert the SN-38G back to the active and toxic SN-38 using bacterial β-glucuronidase enzyme (GUS). T...
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تاریخ انتشار 2014