Parallel strategies for the preparation and selection of liver-targeted glucocorticoid receptor antagonists.
Article Details
- CitationCopy to clipboard
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
Drug Target Property Measurement pH Temperature (°C) Mifepristone Glucocorticoid receptor Ki (nM) 1.1 N/A N/A Details Mifepristone Glucocorticoid receptor Ki (nM) 169 N/A N/A Details Mifepristone Glucocorticoid receptor Ki (nM) 5 N/A N/A Details