Functional characterization of cholera toxin inhibitors using human intestinal organoids

Domenique D. Zomer-van Ommen; Aliaksei V. Pukin; Ou Fu; Linda H C Quarles Van Ufford; Hettie M. Janssens; Jeffrey M. Beekman; Roland J. Pieters

doi:10.1021/acs.jmedchem.6b00770

Functional characterization of cholera toxin inhibitors using human intestinal organoids

Domenique D. Zomer-van Ommen, Aliaksei V. Pukin, Ou Fu, Linda H C Quarles Van Ufford, Hettie M. Janssens, Jeffrey M. Beekman, Roland J. Pieters^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	6968-6972
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	59
Issue number	14
DOIs	https://doi.org/10.1021/acs.jmedchem.6b00770
Publication status	Published - 28 Jul 2016

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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.",

author = "{Zomer-van Ommen}, {Domenique D.} and Pukin, {Aliaksei V.} and Ou Fu and {Quarles Van Ufford}, {Linda H C} and Janssens, {Hettie M.} and Beekman, {Jeffrey M.} and Pieters, {Roland J.}",

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AU - Zomer-van Ommen, Domenique D.

AU - Pukin, Aliaksei V.

AU - Fu, Ou

AU - Quarles Van Ufford, Linda H C

AU - Janssens, Hettie M.

AU - Beekman, Jeffrey M.

AU - Pieters, Roland J.

PY - 2016/7/28

Y1 - 2016/7/28

N2 - 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.

AB - 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.

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DO - 10.1021/acs.jmedchem.6b00770

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VL - 59

SP - 6968

EP - 6972

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 14

ER -

Functional characterization of cholera toxin inhibitors using human intestinal organoids

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