Parallel strategies for the preparation and selection of liver-targeted glucocorticoid receptor antagonists.

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Backes BJ, Hamilton GL, Nguyen P, Wilcox D, Fung S, Wang J, Grynfarb M, Goos-Nilsson A, Jacobson PB, von Geldern TW

Parallel strategies for the preparation and selection of liver-targeted glucocorticoid receptor antagonists.

Bioorg Med Chem Lett. 2007 Jan 1;17(1):40-4. Epub 2006 Oct 5.

PubMed ID
17070047 [ View in PubMed
]
Abstract

Libraries of mifepristone analogs, MP-Acids, were designed and synthesized to increase the chances of identifying GR antagonists that possess liver-selective pharmacological profiles. MP-Acids were uniformly potent GR antagonists in binding and in cell-based functional assays. A high throughput pharmacokinetic selection strategy that employs the cassette dosing of MP-Acids was developed to identify liver-targeting compounds. Thus, resource-intensive in vivo assays to measure liver-selective pharmacology were enriched with GR antagonists that achieve high concentrations in the liver.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MifepristoneGlucocorticoid receptorKi (nM)1.1N/AN/ADetails
MifepristoneGlucocorticoid receptorKi (nM)169N/AN/ADetails
MifepristoneGlucocorticoid receptorKi (nM)5N/AN/ADetails