October 15, 2012PLoS ONEOpen Access

Slow Receptor Dissociation Kinetics Differentiate Macitentan from Other Endothelin Receptor Antagonists in Pulmonary Arterial Smooth Muscle Cells

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Population

Cultured human primary pulmonary arterial smooth muscle cells and CHO cells expressing recombinant ETA or…

Comparison

Macitentan vs Ambrisentan and bosentan

Design

Preclinical

Authors

JGJohn GatfieldIdorsia (Switzerland)CGCelia Mueller GrandjeanIdorsia (Switzerland)TSThomas SasseActelion (Switzerland)

Discussion

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Implication

Should not yet change ERA selection; hypothesis-generating for macitentan’s kinetic profile in human PAH.

Structured PICO

Population

Cultured human primary pulmonary arterial smooth muscle cells (PASMC) and CHO cells expressing recombinant ETA or ETB receptors

Intervention

Macitentan

Comparator

Ambrisentan and bosentan

Outcome

Inhibitory potency (Kb) and receptor inhibition kinetics (association and dissociation rates, receptor occupancy half-life) measured by calcium release and inositol-1-phosphate (IP1) assayssurrogate

Macitentan is a competitive endothelin receptor antagonist with significantly slower receptor dissociation kinetics than bosentan and ambrisentan, leading to insurmountable antagonism in functional assays.

Cite This Study

Gatfield et al. (2012) studied this question.

synapsesocial.com/papers/6a85c66a734852141cd4dfff https://doi.org/10.1371/journal.pone.0047662

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Slow Receptor Dissociation Kinetics Differentiate Macitentan from Other Endothelin Receptor Antagonists in Pulmonary Arterial Smooth Muscle Cells

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Slow Receptor Dissociation Kinetics Differentiate Macitentan from Other Endothelin Receptor Antagonists in Pulmonary Arterial Smooth Muscle Cells

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Also Consider

Also Consider