Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors.

Masashi Mima; Chiemi Mishima-Tsumagari; Mayumi Sakata-Sakuta; Ryo Iwaoka; Kunihiko Iwamoto

doi:10.1107/s2053230x26003432

June 1, 2026

Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors.

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Key Points

The study aims to uncover the binding mode of vornorexant at orexin receptors to understand its high-affinity antagonism.
Structural analysis of vornorexant binding to orexin receptors
Assessment of steric hindrance during binding
Comparison with other orexin receptor antagonists
Vornorexant demonstrates high-affinity dual antagonism without steric hindrance.
The structural basis of dual antagonism supports design strategies for new antagonists.
Insights gained can inform future development of orexin-targeted therapies.

Implication

Structural analysis reveals high-affinity dual antagonism of vornorexant at orexin receptors, suggesting new design strategies for antagonists.

Abstract

R, with no steric hindrance observed, supporting a balanced dual antagonism. These results provide a structural basis for the high-affinity dual antagonism of vornorexant and offer insights for the design of orexin receptor antagonists.

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Cite This Study

Mima et al. (2026) studied this question.

synapsesocial.com/papers/69f594ca71405d493afffa5b https://doi.org/10.1107/s2053230x26003432

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Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors.

Key Points

Implication

Abstract

Discussion

Cite This Study

Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors.

Key Points

Implication

Abstract

Discussion

Cite This Study

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