{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:49:55Z","timestamp":1785408595152,"version":"3.56.0"},"reference-count":34,"publisher":"International Union of Crystallography (IUCr)","issue":"6","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"funder":[{"name":"Taisho Pharmaceutical Co. Ltd"}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr F Struct Biol Commun","Acta Crystallogr F","Acta Crystallogr F Struct Biol Cryst Commun","Acta Cryst F","Acta Cryst F Struct Biol Commun","Acta Cryst Sect F","Acta Cryst Sect F Struct Biol Commun","Acta Crystallogr Sect F","Acta Crystallogr Sect F Struct Biol Commun","Acta Crystallogr Sect F Struct Biol Cryst Commun"],"accepted":{"date-parts":[[2026,4,1]]},"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:p>\n                    Insomnia is a widespread sleep disorder that significantly impairs quality of life and imposes a societal burden. Although benzodiazepines and Z-drugs are commonly used for treating insomnia, these drugs often have side effects, such as excessive muscle relaxation and dependency. The orexin signaling pathway has emerged as a promising therapeutic target for insomnia, with dual orexin receptor antagonists (DORAs) offering an alternative approach to treatment. To reduce the potential of these drugs for next-day residual effects, we developed vornorexant, a novel DORA with a high receptor affinity and a short elimination half-life. In this study, we investigated the molecular interactions of this drug with human orexin receptors through crystal structure analysis of its binding to orexin type 2 receptor (OX\n                    <jats:sub>2<\/jats:sub>\n                    R) and a docking simulation of the drug with orexin type 1 receptor (OX\n                    <jats:sub>1<\/jats:sub>\n                    R). The crystal structure of the OX\n                    <jats:sub>2<\/jats:sub>\n                    R\u2013vornorexant complex revealed a conserved U-shaped conformation stabilized by hydrophobic and hydrogen-bonding interactions, including key contacts with Asn324, His350 and Pro131. OX\n                    <jats:sub>1<\/jats:sub>\n                    R\u2013vornorexant docking simulations indicated a similar binding mode to OX\n                    <jats:sub>1<\/jats:sub>\n                    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.\n                  <\/jats:p>","DOI":"10.1107\/s2053230x26003432","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:06:12Z","timestamp":1776855972000},"page":"201-207","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":0,"title":["Structural insights into the binding mode of the hypnotic drug vornorexant to orexin receptors"],"prefix":"10.1107","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-9129","authenticated-orcid":true,"given":"Masashi","family":"Mima","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033nw2736","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiemi","family":"Mishima-Tsumagari","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033nw2736","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Sakata-Sakuta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033nw2736","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Iwaoka","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033nw2736","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Iwamoto","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033nw2736","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"pg5098_bb100","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1107\/S2059798323003595","volume":"79","author":"Agirre","year":"2023","journal-title":"Acta Cryst. 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