Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid receptor modulator-statin hybrids.
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Link JT, Sorensen BK, Lai C, Wang J, Fung S, Deng D, Emery M, Carroll S, Grynfarb M, Goos-Nilsson A, Von Geldern T
Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid receptor modulator-statin hybrids.
Bioorg Med Chem Lett. 2004 Aug 16;14(16):4173-8.
- PubMed ID
- 15261265 [ View in PubMed]
- Abstract
The synthesis, activity, metabolic stability, and pharmacokinetics of steroidal and nonsteroidal glucocorticoid receptor modulator-statin hybrids is reported. Potent steroidal antagonist-statin hybrids like 22 (h-GR binding IC(50)=7 nM) and nonsteroidal modulator hybrids like 16 (h-GR binding IC(50)=2 nM) were discovered. Appending a 'statin'-like diol-acid group to the modulators dramatically improved metabolic stability (and in some cases hepatocyte activity), but did not impart hepatoselectivity.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Mifepristone Glucocorticoid receptor IC 50 (nM) 1.1 N/A N/A Details Mifepristone Glucocorticoid receptor IC 50 (nM) 4.8 N/A N/A Details Mifepristone Progesterone receptor IC 50 (nM) 2.9 N/A N/A Details