ArticleMolecular pharmacology2020
Weak Microbial Metabolites: a Treasure Trove for Using Biomimicry to Discover and Optimize Drugs.
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Article in Molecular pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2citing papers in PubMed
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Who cites it
2 citing papers in PubMed.
- Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Deciphering structural bases of intestinal and hepatic selectivity in targeting pregnane X receptor with indole-based microbial mimics.Bioorganic chemistry · 2021Article
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Authors and funding
13 authors.
Zdenek DvorakDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).ORCID 0000-0002-3938-3585
Max KlapholzDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
Thomas P BurrisDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
Benjamin P WillingDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
Antimo GioielloDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
Roberto PellicciariDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
Francesco GalliDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
John MarchDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
Stephen J O'KeefeDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
R Balfour SartorDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.) ryan_balfour_sartor@med.unc.edu.
Chang H KimDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.).
Maayan LevyDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.) maayanle@pennmedicine.upenn.edu.
Sridhar ManiDepartment of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania (M.K., M.L.); The Center for Clinical Pharmacology, Washington University in St. Louis and St. Louis College of Pharmacy, St. Louis, Missouri (T.P.B.); Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta (B.P.W.); Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy (A.G., F.G.); TES Pharma, Corso Vannucci, Perugia, Italy (R.P.); The Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York (J.M.); Division of Gastroenterology and Nutrition, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania (S.J.O.); Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (R.B.S.); Department of Pathology, Mary H. Weiser Food Allergy Center, and Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan (C.H.K.); and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (S.M.) sridhar.mani@einsteinmed.org.
Funding
Role of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SARTOR, RYAN B · 2013 to 2023
$17.9MDevelopmental PBDE exposure, gut microbiome, and diabetesR01ES030197 · NIEHS · UNIVERSITY OF WASHINGTON · PI Julia Yue Cui, Haiwei Gu · 2019 to 2026
$5.0MMicrobial Metabolite Mimics, PXR and Colitis-Induced Colorectal CancerR01CA222469 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI MANI, SRIDHAR · 2018 to 2022
$2.3MNCI NIH HHS R01 CA222469NIDDK NIH HHS P01 DK094779NIEHS NIH HHS R01 ES030197
Abstract
For decades, traditional drug discovery has used natural product and synthetic chemistry approaches to generate libraries of compounds, with some ending as promising drug candidates. A complementary approach has been to adopt the concept of biomimicry of natural products and metabolites so as to improve multiple drug-like features of the parent molecule. In this effort, promiscuous and weak interactions between ligands and receptors are often ignored in a drug discovery process. In this Emerging Concepts article, we highlight microbial metabolite mimicry, whereby parent metabolites have weak interactions with their receptors that then have led to discrete examples of more potent and effective drug-like molecules. We show specific examples of parent-metabolite mimics with potent effects in vitro and in vivo. Furthermore, we show examples of emerging microbial ligand-receptor interactions and provide a context in which these ligands could be improved as potential drugs. A balanced conceptual advance is provided in which we also acknowledge potential pitfalls-hyperstimulation of finely balanced receptor-ligand interactions could also be detrimental. However, with balance, we provide examples of where this emerging concept needs to be tested. SIGNIFICANCE STATEMENT: Microbial metabolite mimicry is a novel way to expand on the chemical repertoire of future drugs. The emerging concept is now explained using specific examples of the discovery of therapeutic leads from microbial metabolites.
Indexed as
BacteriaBiological ProductsDrug DiscoveryHumansIndolesLigandsMolecular MimicryBiological ProductsIndolesLigands
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