New Inhibitors for a Key Enzyme in Metabolic Syndrome
Author Information
Author(s): Su Xiangdong, Pradaux-Caggiano Fabienne, Vicker Nigel, Thomas Mark P, Halem Heather, Culler Michael D, Potter Barry V L
Primary Institution: University of Bath
Hypothesis
Can adamantyl ethanone pyridyl derivatives serve as selective inhibitors of human 11β-Hydroxysteroid Dehydrogenase Type 1?
Conclusion
The study identified potent and selective inhibitors of human 11β-HSD1 that may be beneficial for treating metabolic syndrome.
Supporting Evidence
- Lead compounds showed low nanomolar inhibition against human and mouse 11β-HSD1.
- Compounds were selective for 11β-HSD1 with no activity against 11β-HSD2 and 17β-HSD1.
- Structure-activity relationship studies identified key features for inhibitory activity.
- Most potent inhibitors had IC50 values around 34–48 nm against human 11β-HSD1.
- Compounds displayed reasonable metabolic stability in human liver microsomes.
- Selected compounds were tested for activity against mouse 11β-HSD1.
Takeaway
Scientists found new compounds that can help block a specific enzyme linked to diabetes and obesity, which could lead to better treatments.
Methodology
The study involved synthesizing and testing various adamantyl ethanone pyridyl derivatives for their inhibitory effects on human 11β-HSD1 in a cell line.
Limitations
The compounds' solubility in water may pose challenges for in vivo studies.
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website