Alleviating cancer drug toxicity by inhibiting a bacterial enzyme
DC Field | Value | Language |
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dc.contributor.author | Wallace B.D. | - |
dc.contributor.author | Wang H. | - |
dc.contributor.author | Lane K.T. | - |
dc.contributor.author | Scott J.E. | - |
dc.contributor.author | Orans J. | - |
dc.contributor.author | Koo J.S. | - |
dc.contributor.author | Venkatesh M. | - |
dc.contributor.author | Jobin C. | - |
dc.contributor.author | Yeh L.-A. | - |
dc.contributor.author | Mani S. | - |
dc.contributor.author | Redinbo M.R. | - |
dc.date.available | 2020-11-03T07:44:40Z | - |
dc.date.issued | 2010-11 | - |
dc.identifier.issn | 0036-8075 | - |
dc.identifier.issn | 1095-9203 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/15517 | - |
dc.description.abstract | The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy. | - |
dc.format.extent | 5 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | - |
dc.title | Alleviating cancer drug toxicity by inhibiting a bacterial enzyme | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1126/science.1191175 | - |
dc.identifier.scopusid | 2-s2.0-78149295964 | - |
dc.identifier.wosid | 000283855700046 | - |
dc.identifier.bibliographicCitation | Science, v.330, no.6005, pp 831 - 835 | - |
dc.citation.title | Science | - |
dc.citation.volume | 330 | - |
dc.citation.number | 6005 | - |
dc.citation.startPage | 831 | - |
dc.citation.endPage | 835 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | 7 ethyl 10 hydroxycamptothecin | - |
dc.subject.keywordPlus | 7 ethyl 10 hydroxycamptothecin glucuronide | - |
dc.subject.keywordPlus | antineoplastic agent | - |
dc.subject.keywordPlus | beta glucuronidase | - |
dc.subject.keywordPlus | glucaro 1,5 lactam | - |
dc.subject.keywordPlus | glycosidase inhibitor | - |
dc.subject.keywordPlus | irinotecan | - |
dc.subject.keywordPlus | bacterium | - |
dc.subject.keywordPlus | cancer | - |
dc.subject.keywordPlus | cell organelle | - |
dc.subject.keywordPlus | chemotherapy | - |
dc.subject.keywordPlus | diarrheal disease | - |
dc.subject.keywordPlus | drug | - |
dc.subject.keywordPlus | enzyme activity | - |
dc.subject.keywordPlus | functional morphology | - |
dc.subject.keywordPlus | health risk | - |
dc.subject.keywordPlus | inhibition | - |
dc.subject.keywordPlus | inhibitor | - |
dc.subject.keywordPlus | mammal | - |
dc.subject.keywordPlus | microbial activity | - |
dc.subject.keywordPlus | toxicity | - |
dc.subject.keywordPlus | aerobic bacterium | - |
dc.subject.keywordPlus | anaerobic bacterium | - |
dc.subject.keywordPlus | animal experiment | - |
dc.subject.keywordPlus | article | - |
dc.subject.keywordPlus | colon cancer | - |
dc.subject.keywordPlus | crystal structure | - |
dc.subject.keywordPlus | diarrhea | - |
dc.subject.keywordPlus | drug effect | - |
dc.subject.keywordPlus | drug efficacy | - |
dc.subject.keywordPlus | drug structure | - |
dc.subject.keywordPlus | enzyme inhibition | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | in vitro study | - |
dc.subject.keywordPlus | intestine flora | - |
dc.subject.keywordPlus | intestine injury | - |
dc.subject.keywordPlus | mouse | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | priority journal | - |
dc.subject.keywordPlus | Animals | - |
dc.subject.keywordPlus | Antineoplastic Agents, Phytogenic | - |
dc.subject.keywordPlus | Bacteria, Anaerobic | - |
dc.subject.keywordPlus | Camptothecin | - |
dc.subject.keywordPlus | Cell Line, Tumor | - |
dc.subject.keywordPlus | Colon | - |
dc.subject.keywordPlus | Crystallography, X-Ray | - |
dc.subject.keywordPlus | Diarrhea | - |
dc.subject.keywordPlus | Drug Evaluation, Preclinical | - |
dc.subject.keywordPlus | Enzyme Inhibitors | - |
dc.subject.keywordPlus | Escherichia coli | - |
dc.subject.keywordPlus | Escherichia coli Proteins | - |
dc.subject.keywordPlus | Female | - |
dc.subject.keywordPlus | Glucuronidase | - |
dc.subject.keywordPlus | Humans | - |
dc.subject.keywordPlus | Intestinal Mucosa | - |
dc.subject.keywordPlus | Mice | - |
dc.subject.keywordPlus | Mice, Inbred BALB C | - |
dc.subject.keywordPlus | Models, Molecular | - |
dc.subject.keywordPlus | Prodrugs | - |
dc.subject.keywordPlus | Protein Conformation | - |
dc.subject.keywordPlus | Bacteria (microorganisms) | - |
dc.subject.keywordPlus | Mammalia | - |
dc.subject.keywordPlus | Mus | - |
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