Inhibition of the endothelin A receptor with ZD4054
Author Information
Author(s): Morris C D, Rose A, Curwen J, Hughes A M, Wilson D J, Webb D J
Primary Institution: AstraZeneca
Hypothesis
Specific blockade of the endothelin A receptor may have anticancer effects while retaining beneficial effects mediated by the endothelin B receptor.
Conclusion
ZD4054 is a potent and specific antagonist of the endothelin A receptor, with no evidence of endothelin B receptor blockade.
Supporting Evidence
- ZD4054 specifically bound to the endothelin A receptor with high affinity.
- A single oral dose of ZD4054 reduced forearm vasoconstriction in response to endothelin-1.
- Mean plasma endothelin-1 concentrations remained within the placebo reference range after ZD4054 administration.
Takeaway
This study shows that a new drug called ZD4054 can block a specific receptor involved in cancer without affecting another receptor that helps with cell death.
Methodology
The study included receptor-binding assays and two randomized, placebo-controlled trials involving healthy volunteers to assess the effects of ZD4054.
Limitations
The study was limited to a small number of healthy volunteers and specific doses due to the invasive nature of the procedures.
Participant Demographics
Healthy adult male volunteers.
Statistical Information
P-Value
0.021
Confidence Interval
95% CI: 8.23, 8.32 nM
Statistical Significance
p=0.021
Digital Object Identifier (DOI)
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