{"id":"https://openalex.org/W7161982905","doi":"https://doi.org/10.1186/s12916-026-04926-5","title":"Phase 1 randomized trial of HS-10353, a novel GABA(A) positive allosteric modulator for treatment of major depressive disorder","display_name":"Phase 1 randomized trial of HS-10353, a novel GABA(A) positive allosteric modulator for treatment of major depressive disorder","publication_year":2026,"publication_date":"2026-05-21","ids":{"openalex":"https://openalex.org/W7161982905","doi":"https://doi.org/10.1186/s12916-026-04926-5","pmid":"https://pubmed.ncbi.nlm.nih.gov/42169103"},"language":"en","primary_location":{"id":"doi:10.1186/s12916-026-04926-5","doi":"https://doi.org/10.1186/s12916-026-04926-5","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s12916-026-04926-5","pdf_url":null,"source":{"id":"https://openalex.org/S135560524","display_name":"BMC Medicine","issn_l":"1741-7015","issn":["1741-7015"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","doyens","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"BMC Medicine","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1186/s12916-026-04926-5","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5001130861","display_name":"Zhenlei Wang","orcid":"https://orcid.org/0000-0001-8789-4219","observed_orcids":["https://orcid.org/0000-0001-8789-4219"]},"institutions":[{"id":"https://openalex.org/I24185976","display_name":"Sichuan University","ror":"https://ror.org/011ashp19","country_code":"CN","type":"education","lineage":["https://openalex.org/I24185976"]},{"id":"https://openalex.org/I4210089761","display_name":"West China Hospital of Sichuan University","ror":"https://ror.org/007mrxy13","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210089761"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zhenlei Wang","raw_affiliation_strings":["Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China","Mental Health Center, West China Hospital, Sichuan University, Chengdu, China"],"raw_orcid":"https://orcid.org/0000-0001-8789-4219","affiliations":[{"raw_affiliation_string":"Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China","institution_ids":["https://openalex.org/I24185976","https://openalex.org/I4210089761"]},{"raw_affiliation_string":"Mental Health Center, West China Hospital, Sichuan University, Chengdu, China","institution_ids":["https://openalex.org/I24185976"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060951061","display_name":"M Li","orcid":"https://orcid.org/0000-0001-7365-0344","observed_orcids":["https://orcid.org/0000-0001-7365-0344","https://orcid.org/0000-0003-0629-4217","https://orcid.org/0000-0003-0831-332X","https://orcid.org/0000-0003-4229-1697","https://orcid.org/0009-0007-1835-9782"]},"institutions":[{"id":"https://openalex.org/I24185976","display_name":"Sichuan University","ror":"https://ror.org/011ashp19","country_code":"CN","type":"education","lineage":["https://openalex.org/I24185976"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Mingli Li","raw_affiliation_strings":["Mental Health Center, West China Hospital, Sichuan University, Chengdu, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Mental Health Center, West China Hospital, Sichuan University, Chengdu, China","institution_ids":["https://openalex.org/I24185976"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5136648735","display_name":"Xiaojin Xu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Xiaojin Xu","raw_affiliation_strings":["Department of Psychiatry, Wuhan Mental Health Center, Wuhan, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Psychiatry, Wuhan Mental Health Center, Wuhan, China","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5136707438","display_name":"Ruiling Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210101741","display_name":"Henan Psychiatric Hospital","ror":"https://ror.org/015qzwq73","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210101741"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Ruiling Zhang","raw_affiliation_strings":["Department of Psychiatry, Henan Mental Hospital, Xinxiang, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Psychiatry, Henan Mental Hospital, Xinxiang, China","institution_ids":["https://openalex.org/I4210101741"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109258306","display_name":"Huali Lin","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210111546","display_name":"Xian Mental Health Center","ror":"https://ror.org/020299x40","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210111546"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Huali Lin","raw_affiliation_strings":["Xi'an Mental Health Center, Xi'an, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Xi'an Mental Health Center, Xi'an, China","institution_ids":["https://openalex.org/I4210111546"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111209709","display_name":"Fude Yang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I183519381","display_name":"Capital Medical University","ror":"https://ror.org/013xs5b60","country_code":"CN","type":"education","lineage":["https://openalex.org/I183519381"]},{"id":"https://openalex.org/I20231570","display_name":"Peking University","ror":"https://ror.org/02v51f717","country_code":"CN","type":"education","lineage":["https://openalex.org/I20231570"]},{"id":"https://openalex.org/I4210147103","display_name":"Beijing HuiLongGuan Hospital","ror":"https://ror.org/03wgqqb38","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210110145","https://openalex.org/I4210135108","https://openalex.org/I4210147103"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Fude Yang","raw_affiliation_strings":["Beijing HuiLongGuan Hospital, Capital Medical University, Peking University HuiLongGuan Clinical Medical School, Beijing, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Beijing HuiLongGuan Hospital, Capital Medical University, Peking University HuiLongGuan Clinical Medical School, Beijing, China","institution_ids":["https://openalex.org/I183519381","https://openalex.org/I20231570","https://openalex.org/I4210147103"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5141094949","display_name":"Jie Qi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jie Qi","raw_affiliation_strings":["Shanghai Hansoh BioMedical Co., Ltd., Shanghai, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shanghai Hansoh BioMedical Co., Ltd., Shanghai, China","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5141058133","display_name":"Huifeng Zhang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Huifeng Zhang","raw_affiliation_strings":["Shanghai Hansoh BioMedical Co., Ltd., Shanghai, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shanghai Hansoh BioMedical Co., Ltd., Shanghai, China","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5136716241","display_name":"Yuying Tao","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yuying Tao","raw_affiliation_strings":["Shanghai Hansoh BioMedical Co., Ltd., Shanghai, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shanghai Hansoh BioMedical Co., Ltd., Shanghai, China","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5079855421","display_name":"Qi Shen","orcid":"https://orcid.org/0000-0003-0238-6085","observed_orcids":["https://orcid.org/0000-0003-0238-6085"]},"institutions":[{"id":"https://openalex.org/I24185976","display_name":"Sichuan University","ror":"https://ror.org/011ashp19","country_code":"CN","type":"education","lineage":["https://openalex.org/I24185976"]},{"id":"https://openalex.org/I4210089761","display_name":"West China Hospital of Sichuan University","ror":"https://ror.org/007mrxy13","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210089761"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Qi Shen","raw_affiliation_strings":["Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China. 769824157@qq.com","Mental Health Center, West China Hospital, Sichuan University, Chengdu, China. 769824157@qq.com"],"raw_orcid":"https://orcid.org/0000-0003-0238-6085","affiliations":[{"raw_affiliation_string":"Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China. 769824157@qq.com","institution_ids":["https://openalex.org/I24185976","https://openalex.org/I4210089761"]},{"raw_affiliation_string":"Mental Health Center, West China Hospital, Sichuan University, Chengdu, China. 769824157@qq.com","institution_ids":["https://openalex.org/I24185976","https://openalex.org/I4210089761"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5079855421"],"corresponding_institution_ids":["https://openalex.org/I24185976","https://openalex.org/I4210089761"],"apc_list":{"value":4190,"currency":"USD","value_usd":4190},"apc_paid":{"value":4190,"currency":"USD","value_usd":4190},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.40404493,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"24","issue":"1","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11071","display_name":"Treatment of Major Depression","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11071","display_name":"Treatment of Major Depression","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11337","display_name":"Tryptophan and brain disorders","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2803","display_name":"Biological Psychiatry"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/major-depressive-disorder","display_name":"major depressive disorder","score":0.8899999856948853},{"id":"https://openalex.org/keywords/antidepressant-efficacy","display_name":"antidepressant efficacy","score":0.5070000290870667},{"id":"https://openalex.org/keywords/safety-and-tolerability","display_name":"safety and tolerability","score":0.8569999933242798},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.9869999885559082},{"id":"https://openalex.org/keywords/single-ascending-dose","display_name":"single ascending dose","score":0.7379999756813049},{"id":"https://openalex.org/keywords/multiple-ascending-dose","display_name":"multiple ascending dose","score":0.9860000014305115},{"id":"https://openalex.org/keywords/hamilton-depression-rating-scale","display_name":"Hamilton Depression Rating Scale","score":0.7599999904632568},{"id":"https://openalex.org/keywords/once-daily-dosing","display_name":"once-daily dosing","score":0.7590000033378601},{"id":"https://openalex.org/keywords/healthy-volunteers","display_name":"healthy volunteers","score":0.5249999761581421},{"id":"https://openalex.org/keywords/depression-treatment","display_name":"depression treatment","score":0.414000004529953},{"id":"https://openalex.org/keywords/gaba-a-receptor-agonists","display_name":"GABA-A receptor agonists","score":0.4880000054836273},{"id":"https://openalex.org/keywords/sleepiness","display_name":"sleepiness","score":0.5960000157356262},{"id":"https://openalex.org/keywords/alanine-aminotransferase","display_name":"alanine aminotransferase","score":0.859000027179718}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8996000289916992},{"id":"https://openalex.org/C2778375690","wikidata":"https://www.wikidata.org/wiki/Q7814214","display_name":"Tolerability","level":3,"score":0.796500027179718},{"id":"https://openalex.org/C2780051608","wikidata":"https://www.wikidata.org/wiki/Q42844","display_name":"Major depressive disorder","level":3,"score":0.7501000165939331},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.6769000291824341},{"id":"https://openalex.org/C27081682","wikidata":"https://www.wikidata.org/wiki/Q269829","display_name":"Placebo","level":3,"score":0.6171000003814697},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5677000284194946},{"id":"https://openalex.org/C168563851","wikidata":"https://www.wikidata.org/wiki/Q1436668","display_name":"Randomized controlled trial","level":2,"score":0.5544000267982483},{"id":"https://openalex.org/C203092338","wikidata":"https://www.wikidata.org/wiki/Q1340863","display_name":"Clinical endpoint","level":3,"score":0.5169000029563904},{"id":"https://openalex.org/C72563966","wikidata":"https://www.wikidata.org/wiki/Q1303415","display_name":"Cohort","level":2,"score":0.4595000147819519},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.37470000982284546},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3736000061035156},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.37040001153945923},{"id":"https://openalex.org/C2776867660","wikidata":"https://www.wikidata.org/wiki/Q1814941","display_name":"Depression (economics)","level":2,"score":0.3596000075340271},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3366999924182892},{"id":"https://openalex.org/C204243189","wikidata":"https://www.wikidata.org/wiki/Q1363085","display_name":"Randomization","level":3,"score":0.3328999876976013},{"id":"https://openalex.org/C2776466505","wikidata":"https://www.wikidata.org/wiki/Q385555","display_name":"Hamilton Rating Scale for Depression","level":4,"score":0.31679999828338623},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.3125},{"id":"https://openalex.org/C31760486","wikidata":"https://www.wikidata.org/wiki/Q7180990","display_name":"Phases of clinical research","level":3,"score":0.31220000982284546},{"id":"https://openalex.org/C2779034229","wikidata":"https://www.wikidata.org/wiki/Q1077823","display_name":"Somnolence","level":3,"score":0.28679999709129333},{"id":"https://openalex.org/C141341695","wikidata":"https://www.wikidata.org/wiki/Q2368661","display_name":"Surrogate endpoint","level":2,"score":0.2863999903202057},{"id":"https://openalex.org/C201903717","wikidata":"https://www.wikidata.org/wiki/Q1778788","display_name":"Cohort study","level":2,"score":0.27880001068115234},{"id":"https://openalex.org/C2778488018","wikidata":"https://www.wikidata.org/wiki/Q42395","display_name":"White blood cell","level":2,"score":0.25049999356269836}],"mesh":[{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000494","descriptor_name":"Allosteric Regulation","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000928","descriptor_name":"Antidepressive Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D003865","descriptor_name":"Major Depressive Disorder","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D003865","descriptor_name":"Major Depressive Disorder","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D003865","descriptor_name":"Major Depressive Disorder","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D003865","descriptor_name":"Major Depressive Disorder","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D003865","descriptor_name":"Major Depressive Disorder","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D003865","descriptor_name":"Major Depressive Disorder","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D004311","descriptor_name":"Double-Blind Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004311","descriptor_name":"Double-Blind Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004311","descriptor_name":"Double-Blind Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004311","descriptor_name":"Double-Blind Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004311","descriptor_name":"Double-Blind Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004311","descriptor_name":"Double-Blind Method","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011963","descriptor_name":"Receptors, GABA-A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055815","descriptor_name":"Young Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055815","descriptor_name":"Young Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055815","descriptor_name":"Young Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055815","descriptor_name":"Young Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055815","descriptor_name":"Young Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055815","descriptor_name":"Young Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1186/s12916-026-04926-5","doi":"https://doi.org/10.1186/s12916-026-04926-5","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s12916-026-04926-5","pdf_url":null,"source":{"id":"https://openalex.org/S135560524","display_name":"BMC Medicine","issn_l":"1741-7015","issn":["1741-7015"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","doyens","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"BMC Medicine","raw_type":"journal-article"},{"id":"pmid:42169103","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42169103","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"BMC medicine","raw_type":"Journal Article"},{"id":"pmh:oai:doaj.org/article:326a38e42d0841529dab4f37e117ddfd","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/326a38e42d0841529dab4f37e117ddfd","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"BMC Medicine, Vol 24, Iss 1 (2026)","raw_type":"article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13374185","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13374185/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"BMC Med","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1186/s12916-026-04926-5","doi":"https://doi.org/10.1186/s12916-026-04926-5","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s12916-026-04926-5","pdf_url":null,"source":{"id":"https://openalex.org/S135560524","display_name":"BMC Medicine","issn_l":"1741-7015","issn":["1741-7015"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","doyens","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"BMC Medicine","raw_type":"journal-article"},"sustainable_development_goals":[{"score":1.0,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"score":0.8400234580039978,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Randomized Controlled Trial","id":"https://openalex.org/study-designs/randomized-controlled-trial"},{"display_name":"Clinical Trial","id":"https://openalex.org/study-designs/clinical-trial"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":21,"referenced_works":["https://openalex.org/W1993028502","https://openalex.org/W1994727329","https://openalex.org/W2057823239","https://openalex.org/W2076682630","https://openalex.org/W2972149772","https://openalex.org/W2972225326","https://openalex.org/W4211263234","https://openalex.org/W4318918369","https://openalex.org/W4382135413","https://openalex.org/W4385261190","https://openalex.org/W4385264693","https://openalex.org/W4385554004","https://openalex.org/W4385751511","https://openalex.org/W4386424319","https://openalex.org/W4386739180","https://openalex.org/W4389009157","https://openalex.org/W4391469904","https://openalex.org/W4395480631","https://openalex.org/W4400368965","https://openalex.org/W4411932553","https://openalex.org/W4416312220"],"related_works":[],"abstract_inverted_index":{"BACKGROUND:":[0],"HS-10353":[1,59,81,161,223,254,297],"is":[2,14,27,333],"a":[3,28,65,136,232,256,304],"novel":[4],"positive":[5,174],"allosteric":[6],"modulator":[7],"of":[8,20,51,73,102,118,222,234,245,259,296],"\u03b3-aminobutyric":[9],"acid":[10],"A":[11],"receptors":[12],"that":[13,211,324],"under":[15],"development":[16],"for":[17,85,124,224],"the":[18,98,108,112,115,119,148,160,180,191,216],"treatment":[19,154],"major":[21],"depressive":[22],"disorder":[23],"(MDD).":[24],"METHODS:":[25],"This":[26],"double-blind,":[29],"randomized,":[30],"placebo-controlled,":[31],"phase":[32],"1":[33],"trial":[34,332],"comprising":[35],"single":[36],"ascending":[37,42],"dose":[38,43,162,284],"(SAD)":[39],"and":[40,100,143,175,188,202,292,300,341],"multiple":[41,293],"(MAD)":[44],"parts.":[45],"In":[46,68],"SAD,":[47],"8":[48,250],"healthy":[49,141],"volunteers":[50],"each":[52,74],"cohort":[53,75],"were":[54,76,198,204,298],"randomized":[55,77],"(6:2)":[56],"to":[57,79,87,96,200,213,239,252,261,272],"receive":[58,80],"(2-55":[60],"mg)":[61],"or":[62,90,209],"placebo":[63],"in":[64,107,114,159,165,179,190,241,310,320],"fasted":[66],"state.":[67],"MAD,":[69],"12":[70],"MDD":[71,145,323],"patients":[72,321],"(9:3)":[78],"(15-65":[82],"mg/day":[83],"given":[84],"up":[86],"7":[88,226],"days)":[89],"placebo.":[91,253],"The":[92,104,150,308,331],"primary":[93],"objective":[94],"was":[95,133,280],"assess":[97],"safety":[99],"tolerability":[101],"HS-10353.":[103],"efficacy":[105],"endpoint":[106],"MAD":[109,192],"part":[110],"included":[111,169],"change":[113,242],"total":[116],"score":[117,247],"17-item":[120],"Hamilton":[121],"Rating":[122],"Scale":[123],"Depression":[125],"(HAM-D17)":[126],"at":[127,282,335],"day":[128,249],"8.":[129],"Pharmacokinetic":[130],"(PK)":[131],"analysis":[132],"performed":[134],"as":[135],"secondary":[137],"objective.":[138],"RESULTS:":[139],"Forty-eight":[140],"participants":[142,146],"forty-eight":[144],"completed":[147],"study.":[149],"most":[151],"frequently":[152],"observed":[153,281],"emergent":[155],"adverse":[156,195,207],"events":[157,196,208],"(TEAEs)":[158],"groups":[163],"(occurring":[164],"\u2265":[166],"3":[167],"cases)":[168],"white":[170,183],"blood":[171,184],"cells":[172],"urine":[173],"alanine":[176],"aminotransferase":[177],"increased":[178],"SAD":[181],"part,":[182],"cell":[185],"count":[186],"decreased":[187],"somnolence":[189],"part.":[193],"All":[194],"(AEs)":[197],"mild":[199],"moderate,":[201],"there":[203],"no":[205],"serious":[206],"AEs":[210],"led":[212],"withdrawal":[214],"from":[215,243],"trial.":[217],"Treatment":[218],"with":[219,231,264,303,322],"50":[220],"mg":[221],"only":[225],"days":[227],"showed":[228],"therapeutic":[229],"effects,":[230],"difference":[233],"-4.7":[235],"(95%":[236],"CI:":[237],"-8.9":[238],"-0.5)":[240],"baseline":[244],"HAM-D17":[246],"on":[248],"compared":[251],"exhibited":[255],"terminal":[257],"half-life":[258],"14":[260],"22":[262],"h":[263],"minimal":[265],"accumulation":[266],"upon":[267],"repeat":[268],"dosing":[269],"(approximately":[270],"1.3-":[271],"2.5-fold),":[273],"supporting":[274],"once-daily":[275],"dosing;":[276],"while":[277],"absorption":[278],"saturation":[279],"fasting":[283],"levels":[285],"greater":[286],"than":[287],"45":[288],"mg.":[289],"CONCLUSIONS:":[290],"Single":[291],"oral":[294],"doses":[295],"safe":[299],"well":[301],"tolerated":[302],"favorable":[305],"PK":[306],"profile.":[307],"findings":[309],"this":[311],"small,":[312],"short":[313],"duration":[314],"study":[315],"suggest":[316],"an":[317],"early":[318],"signal":[319],"should":[325],"be":[326],"further":[327],"investigated.":[328],"TRIAL":[329],"REGISTRATION:":[330],"registered":[334],"China":[336],"Drug":[337],"Trials":[338],"(CTR20210105,":[339],"2021-01-21)":[340],"ClinicalTrials.gov":[342],"(NCT05195203,":[343],"2022-01-13).":[344]},"counts_by_year":[],"updated_date":"2026-09-29T14:09:16.559479","created_date":"2026-05-22T00:00:00"}