title: Functional Characterization of Cholera Toxin Inhibitors Using Human Intestinal Organoids.
abstract: Preclinical drug testing in primary human cell models that recapitulate disease can significantly reduce animal experimentation and time-to-the-clinic. We used intestinal organoids to quantitatively study the potency of multivalent cholera toxin inhibitors. The method enabled the determination of IC50 values over a wide range of potencies (15 pM to 9 mM). The results indicate for the first time that an organoid-based swelling assay is a useful preclinical method to evaluate inhibitor potencies of drugs that target pathogen-derived toxins.
authors.affiliation: Department of Pediatric Pulmonology, University Medical Centre Utrecht , Lundlaan 6, 3508 GA Utrecht, The Netherlands.
authors.forename: Domenique D
authors.initials: DD
authors.lastname: Zomer-van Ommen
authors.affiliation: Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Aliaksei V
authors.initials: AV
authors.lastname: Pukin
authors.affiliation: Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Ou
authors.initials: O
authors.lastname: Fu
authors.affiliation: Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Linda H C
authors.initials: LH
authors.lastname: Quarles van Ufford
authors.affiliation: Department of Pediatric Pulmonology, Erasmus Medical Center/Sophia Children's Hospital , Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Hettie M
authors.initials: HM
authors.lastname: Janssens
authors.affiliation: Department of Pediatric Pulmonology, University Medical Centre Utrecht , Lundlaan 6, 3508 GA Utrecht, The Netherlands.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Beekman
authors.affiliation: Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Pieters
mesh_terms: D000992:Antitoxins / Q000737:chemistry / Q000494:pharmacology*; D002772:Cholera Toxin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007422:Intestines / Q000187:drug effects*; D015394:Molecular Structure; D009940:Organoids / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000992:Antitoxins; D002772:Cholera Toxin