Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-09-10DOI: 10.1016/j.chembiol.2015.08.006
Georgios Pantouris, Mansoor Ali Syed, Chengpeng Fan, Deepa Rajasekaran, Thomas Yoonsang Cho, Eric M Rosenberg, Richard Bucala, Vineet Bhandari, Elias J Lolis
{"title":"An Analysis of MIF Structural Features that Control Functional Activation of CD74.","authors":"Georgios Pantouris, Mansoor Ali Syed, Chengpeng Fan, Deepa Rajasekaran, Thomas Yoonsang Cho, Eric M Rosenberg, Richard Bucala, Vineet Bhandari, Elias J Lolis","doi":"10.1016/j.chembiol.2015.08.006","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.006","url":null,"abstract":"<p><p>For more than 15 years, the tautomerase active site of macrophage migration inhibitory factor (MIF) and its catalytic residue Pro1 have been being targeted for the development of therapeutics that block activation of its cell surface receptor, CD74. Neither the biological role of the MIF catalytic site nor the mechanistic details of CD74 activation are well understood. The inherently unstable structure of CD74 remains the biggest obstacle in structural studies with MIF for understanding the basis of CD74 activation. Using a novel approach, we elucidate the mechanistic details that control activation of CD74 by MIF surface residues and identify structural parameters of inhibitors that reduce CD74 biological activation. We also find that N-terminal mutants located deep in the catalytic site affect surface residues immediately outside the catalytic site, which are responsible for reduction of CD74 activation. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1197-205"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34066918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-08-27DOI: 10.1016/j.chembiol.2015.07.018
Elizabeth Anscombe, Elisa Meschini, Regina Mora-Vidal, Mathew P Martin, David Staunton, Matthis Geitmann, U Helena Danielson, Will A Stanley, Lan Z Wang, Tristan Reuillon, Bernard T Golding, Celine Cano, David R Newell, Martin E M Noble, Stephen R Wedge, Jane A Endicott, Roger J Griffin
{"title":"Identification and Characterization of an Irreversible Inhibitor of CDK2.","authors":"Elizabeth Anscombe, Elisa Meschini, Regina Mora-Vidal, Mathew P Martin, David Staunton, Matthis Geitmann, U Helena Danielson, Will A Stanley, Lan Z Wang, Tristan Reuillon, Bernard T Golding, Celine Cano, David R Newell, Martin E M Noble, Stephen R Wedge, Jane A Endicott, Roger J Griffin","doi":"10.1016/j.chembiol.2015.07.018","DOIUrl":"10.1016/j.chembiol.2015.07.018","url":null,"abstract":"<p><p>Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1159-64"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33963731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-09-10DOI: 10.1016/j.chembiol.2015.08.008
Lian Yang, Ashraf Ibrahim, Chad W Johnston, Michael A Skinnider, Bin Ma, Nathan A Magarvey
{"title":"Exploration of Nonribosomal Peptide Families with an Automated Informatic Search Algorithm.","authors":"Lian Yang, Ashraf Ibrahim, Chad W Johnston, Michael A Skinnider, Bin Ma, Nathan A Magarvey","doi":"10.1016/j.chembiol.2015.08.008","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.008","url":null,"abstract":"<p><p>Microbial natural products are some of the most important pharmaceutical agents and possess unparalleled chemical diversity. Here we present an untargeted metabolomics algorithm that builds on our validated iSNAP platform to rapidly identify families of peptide natural products. By utilizing known or in silico-dereplicated seed structures, this algorithm screens tandem mass spectrometry data to elaborate extensive molecular families within crude microbial culture extracts with high confidence and statistical significance. Analysis of peptide natural product producers revealed an abundance of unreported congeners, revealing one of the largest families of natural products described to date, as well as a novel variant with greater potency. These findings demonstrate the effectiveness of the iSNAP platform as an accurate tool for rapidly profiling large families of nonribosomal peptides.</p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1259-69"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34000385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eun Ju Choi, Sang-Jip Nam, Lauren Paul, Deanna Beatty, Christopher A Kauffman, Paul R Jensen, William Fenical
{"title":"Previously Uncultured Marine Bacteria Linked to Novel Alkaloid Production.","authors":"Eun Ju Choi, Sang-Jip Nam, Lauren Paul, Deanna Beatty, Christopher A Kauffman, Paul R Jensen, William Fenical","doi":"10.1016/j.chembiol.2015.07.014","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.014","url":null,"abstract":"<p><p>Low-nutrient media and long incubation times facilitated the cultivation of 20 taxonomically diverse Gram-negative marine bacteria within the phyla Bacteroidetes and Proteobacteria. These strains comprise as many as three new families and include members of clades that had only been observed using culture-independent techniques. Chemical studies of the type strains representing two new families within the order Cytophagales led to the isolation of nine new alkaloid secondary metabolites that can be grouped into four distinct structure classes, including azepinones, aziridines, quinolones, and pyrazinones. Several of these compounds possess antibacterial properties and appear, on structural grounds, to be produced by amino acid-based biosynthetic pathways. Our results demonstrate that relatively simple cultivation techniques can lead to the isolation of new bacterial taxa that are capable of the production of alkaloid secondary metabolites with antibacterial activities. These findings support continued investment in cultivation techniques as a method for natural product discovery. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 9","pages":"1270-9"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9578443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-09-10DOI: 10.1016/j.chembiol.2015.08.009
Nicolas Jacquier, Antonio Frandi, Patrick H Viollier, Gilbert Greub
{"title":"Disassembly of a Medial Transenvelope Structure by Antibiotics during Intracellular Division.","authors":"Nicolas Jacquier, Antonio Frandi, Patrick H Viollier, Gilbert Greub","doi":"10.1016/j.chembiol.2015.08.009","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.009","url":null,"abstract":"<p><p>Chlamydiales possess a minimal but functional peptidoglycan precursor biosynthetic and remodeling pathway involved in the assembly of the division septum by an atypical cytokinetic machine and cryptic or modified peptidoglycan-like structure (PGLS). How this reduced cytokinetic machine collectively coordinates the invagination of the envelope has not yet been explored in Chlamydiales. In other Gram-negative bacteria, peptidoglycan provides anchor points that connect the outer membrane to the peptidoglycan during constriction using the Pal-Tol complex. Purifying PGLS and associated proteins from the chlamydial pathogen Waddlia chondrophila, we unearthed the Pal protein as a peptidoglycan-binding protein that localizes to the chlamydial division septum along with other components of the Pal-Tol complex. Together, our PGLS characterization and peptidoglycan-binding assays support the notion that diaminopimelic acid is an important determinant recruiting Pal to the division plane to coordinate the invagination of all envelope layers with the conserved Pal-Tol complex, even during osmotically protected intracellular growth.</p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1217-27"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34066919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-08-20DOI: 10.1016/j.chembiol.2015.07.015
Hideki Watanabe, Shinya Honda
{"title":"Adaptive Assembly: Maximizing the Potential of a Given Functional Peptide with a Tailor-Made Protein Scaffold.","authors":"Hideki Watanabe, Shinya Honda","doi":"10.1016/j.chembiol.2015.07.015","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.015","url":null,"abstract":"<p><p>Protein engineering that exploits known functional peptides holds great promise for generating novel functional proteins. Here we propose a combinatorial approach, termed adaptive assembly, which provides a tailor-made protein scaffold for a given functional peptide. A combinatorial library was designed to create a tailor-made scaffold, which was generated from β hairpins derived from a 10-residue minimal protein \"chignolin\" and randomized amino acid sequences. We applied adaptive assembly to a peptide with low affinity for the Fc region of human immunoglobulin G, generating a 54-residue protein AF.p17 with a 40,600-fold enhanced affinity. The crystal structure of AF.p17 complexed with the Fc region revealed that the scaffold fixed the active conformation with a unique structure composed of a short α helix, β hairpins, and a loop-like structure. Adaptive assembly can take full advantage of known peptides as assets for generating novel functional proteins. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1165-73"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33945018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-09-10DOI: 10.1016/j.chembiol.2015.06.025
Deborah M Rothman, Xiaolin Gao, Elizabeth George, Timothy Rasmusson, Diksha Bhatia, Irina Alimov, Louis Wang, Amin Kamel, Panagiotis Hatsis, Yan Feng, Antonin Tutter, Gregory Michaud, Earl McDonald, Kavitha Venkatesan, David Farley, Mary Ellen Digan, Yucheng Ni, Fred Harbinski, Mithat Gunduz, Christopher J Wilson, Alan Buckler, Mark Labow, John Tallarico, Vic E Myer, Jeffrey A Porter, Shaowen Wang
{"title":"Metabolic Enzyme Sulfotransferase 1A1 Is the Trigger for N-Benzyl Indole Carbinol Tumor Growth Suppression.","authors":"Deborah M Rothman, Xiaolin Gao, Elizabeth George, Timothy Rasmusson, Diksha Bhatia, Irina Alimov, Louis Wang, Amin Kamel, Panagiotis Hatsis, Yan Feng, Antonin Tutter, Gregory Michaud, Earl McDonald, Kavitha Venkatesan, David Farley, Mary Ellen Digan, Yucheng Ni, Fred Harbinski, Mithat Gunduz, Christopher J Wilson, Alan Buckler, Mark Labow, John Tallarico, Vic E Myer, Jeffrey A Porter, Shaowen Wang","doi":"10.1016/j.chembiol.2015.06.025","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.06.025","url":null,"abstract":"<p><p>In an attempt to identify novel therapeutics and mechanisms to differentially kill tumor cells using phenotypic screening, we identified N-benzyl indole carbinols (N-BICs), synthetic analogs of the natural product indole-3-carbinol (I3C). To understand the mode of action for the molecules we employed Cancer Cell Line Encyclopedia viability profiling and correlative informatics analysis to identify and ultimately confirm the phase II metabolic enzyme sulfotransferase 1A1 (SULT1A1) as the essential factor for compound selectivity. Further studies demonstrate that SULT1A1 activates the N-BICs by rendering the compounds strong electrophiles which can alkylate cellular proteins and thereby induce cell death. This study demonstrates that the selectivity profile for N-BICs is through conversion by SULT1A1 from an inactive prodrug to an active species that induces cell death and tumor suppression. </p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1228-37"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.06.025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34000384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenyi Li, Neil M O'Brien-Simpson, Julien Tailhades, Namfon Pantarat, Raymond M Dawson, Laszlo Otvos, Eric C Reynolds, Frances Separovic, Mohammed Akhter Hossain, John D Wade
{"title":"Multimerization of a Proline-Rich Antimicrobial Peptide, Chex-Arg20, Alters Its Mechanism of Interaction with the Escherichia coli Membrane.","authors":"Wenyi Li, Neil M O'Brien-Simpson, Julien Tailhades, Namfon Pantarat, Raymond M Dawson, Laszlo Otvos, Eric C Reynolds, Frances Separovic, Mohammed Akhter Hossain, John D Wade","doi":"10.1016/j.chembiol.2015.08.011","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.011","url":null,"abstract":"<p><p>A3-APO, a de novo designed branched dimeric proline-rich antimicrobial peptide (PrAMP), is highly effective against a variety of in vivo bacterial infections. We undertook a selective examination of the mechanism for the Gram-negative Escherichia coli bacterial membrane interaction of the monomer (Chex-Arg20), dimer (A3-APO), and tetramer (A3-APO disulfide-linked dimer). All three synthetic peptides were effective at killing E. coli. However, the tetramer was 30-fold more membrane disruptive than the dimer while the monomer showed no membrane activity. Using flow cytometry and high-resolution fluorescent microscopy, it was observed that dimerization and tetramerization of the Chex-Arg20 monomer led to an alteration in the mechanism of action from non-lytic/membrane hyperpolarization to membrane disruption/depolarization. Our findings show that the membrane interaction and permeability of Chex-Arg20 was altered by multimerization.</p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1250-8"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34016887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-08-27DOI: 10.1016/j.chembiol.2015.07.017
Peter Canning, Qui Ruan, Tobias Schwerd, Matous Hrdinka, Jenny L Maki, Danish Saleh, Chalada Suebsuwong, Soumya Ray, Paul E Brennan, Gregory D Cuny, Holm H Uhlig, Mads Gyrd-Hansen, Alexei Degterev, Alex N Bullock
{"title":"Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.","authors":"Peter Canning, Qui Ruan, Tobias Schwerd, Matous Hrdinka, Jenny L Maki, Danish Saleh, Chalada Suebsuwong, Soumya Ray, Paul E Brennan, Gregory D Cuny, Holm H Uhlig, Mads Gyrd-Hansen, Alexei Degterev, Alex N Bullock","doi":"10.1016/j.chembiol.2015.07.017","DOIUrl":"10.1016/j.chembiol.2015.07.017","url":null,"abstract":"<p><p>RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers.</p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1174-84"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34029775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry & biologyPub Date : 2015-09-17Epub Date: 2015-09-10DOI: 10.1016/j.chembiol.2015.08.005
Bret D Wallace, Adam B Roberts, Rebecca M Pollet, James D Ingle, Kristen A Biernat, Samuel J Pellock, Madhu Kumar Venkatesh, Leah Guthrie, Sara K O'Neal, Sara J Robinson, Makani Dollinger, Esteban Figueroa, Sarah R McShane, Rachel D Cohen, Jian Jin, Stephen V Frye, William C Zamboni, Charles Pepe-Ranney, Sridhar Mani, Libusha Kelly, Matthew R Redinbo
{"title":"Structure and Inhibition of Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity.","authors":"Bret D Wallace, Adam B Roberts, Rebecca M Pollet, James D Ingle, Kristen A Biernat, Samuel J Pellock, Madhu Kumar Venkatesh, Leah Guthrie, Sara K O'Neal, Sara J Robinson, Makani Dollinger, Esteban Figueroa, Sarah R McShane, Rachel D Cohen, Jian Jin, Stephen V Frye, William C Zamboni, Charles Pepe-Ranney, Sridhar Mani, Libusha Kelly, Matthew R Redinbo","doi":"10.1016/j.chembiol.2015.08.005","DOIUrl":"10.1016/j.chembiol.2015.08.005","url":null,"abstract":"<p><p>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, and the characterization of a β-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the β-glucuronidase active site. Finally, we establish that β-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial β-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity.</p>","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1238-49"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575908/pdf/nihms-718098.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34000386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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