{"id":"https://openalex.org/W7225793409","doi":"https://doi.org/10.1038/s41598-026-79009-9","title":"Podophyllotoxin disrupts the XIAP\u2013caspase-9 interaction to promote apoptosis: insights from a quantitative split-luciferase complementation assay","display_name":"Podophyllotoxin disrupts the XIAP\u2013caspase-9 interaction to promote apoptosis: insights from a quantitative split-luciferase complementation assay","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225793409","doi":"https://doi.org/10.1038/s41598-026-79009-9"},"language":"en","primary_location":{"id":"doi:10.1038/s41598-026-79009-9","doi":"https://doi.org/10.1038/s41598-026-79009-9","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-79009-9","pdf_url":"https://www.nature.com/articles/s41598-026-79009-9_reference.pdf","source":{"id":"https://openalex.org/S196734849","display_name":"Scientific Reports","issn_l":"2045-2322","issn":["2045-2322"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Scientific Reports","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.nature.com/articles/s41598-026-79009-9_reference.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5086592473","display_name":"Katrin Ebrahimi","orcid":"https://orcid.org/0000-0001-5595-8425","observed_orcids":["https://orcid.org/0000-0001-5595-8425"]},"institutions":[{"id":"https://openalex.org/I1516879","display_name":"Tarbiat Modares University","ror":"https://ror.org/03mwgfy56","country_code":"IR","type":"education","lineage":["https://openalex.org/I1516879"]}],"countries":["IR"],"is_corresponding":false,"raw_author_name":"Katrin Ebrahimi","raw_affiliation_strings":["Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran","institution_ids":["https://openalex.org/I1516879"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068956337","display_name":"Farangis Ataei","orcid":"https://orcid.org/0000-0001-8682-9503","observed_orcids":["https://orcid.org/0000-0001-8682-9503"]},"institutions":[{"id":"https://openalex.org/I1516879","display_name":"Tarbiat Modares University","ror":"https://ror.org/03mwgfy56","country_code":"IR","type":"education","lineage":["https://openalex.org/I1516879"]}],"countries":["IR"],"is_corresponding":true,"raw_author_name":"Farangis Ataei","raw_affiliation_strings":["Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran"],"raw_orcid":"https://orcid.org/0000-0001-8682-9503","affiliations":[{"raw_affiliation_string":"Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran","institution_ids":["https://openalex.org/I1516879"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5002216274","display_name":"Saman Hosseinkhani","orcid":"https://orcid.org/0000-0002-0345-7909","observed_orcids":["https://orcid.org/0000-0002-0345-7909"]},"institutions":[{"id":"https://openalex.org/I1516879","display_name":"Tarbiat Modares University","ror":"https://ror.org/03mwgfy56","country_code":"IR","type":"education","lineage":["https://openalex.org/I1516879"]}],"countries":["IR"],"is_corresponding":false,"raw_author_name":"Saman Hosseinkhani","raw_affiliation_strings":["Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran","institution_ids":["https://openalex.org/I1516879"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5068956337"],"corresponding_institution_ids":["https://openalex.org/I1516879"],"apc_list":{"value":2690,"currency":"USD","value_usd":2690},"apc_paid":{"value":2690,"currency":"USD","value_usd":2690},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10294","display_name":"Cell death mechanisms and regulation","score":0.9800000190734863,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10294","display_name":"Cell death mechanisms and regulation","score":0.9800000190734863,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12360","display_name":"Plant-derived Lignans Synthesis and Bioactivity","score":0.017899999395012856,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13026","display_name":"Natural Compounds in Disease Treatment","score":0.0005000000237487257,"subfield":{"id":"https://openalex.org/subfields/2707","display_name":"Complementary and alternative medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C2778143360","wikidata":"https://www.wikidata.org/wiki/Q421193","display_name":"Podophyllotoxin","level":2,"score":0.8698999881744385},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.6862000226974487},{"id":"https://openalex.org/C33195913","wikidata":"https://www.wikidata.org/wiki/Q20970121","display_name":"XIAP","level":5,"score":0.6604999899864197},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.630299985408783},{"id":"https://openalex.org/C115867849","wikidata":"https://www.wikidata.org/wiki/Q753175","display_name":"Protein-fragment complementation assay","level":5,"score":0.6294999718666077},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.5982999801635742},{"id":"https://openalex.org/C188082640","wikidata":"https://www.wikidata.org/wiki/Q1780899","display_name":"Complementation","level":4,"score":0.4512999951839447},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4433000087738037},{"id":"https://openalex.org/C123243835","wikidata":"https://www.wikidata.org/wiki/Q863465","display_name":"Bimolecular fluorescence complementation","level":3,"score":0.43860000371932983},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3693000078201294},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3675000071525574},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.3582000136375427},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.33709999918937683},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.3336000144481659},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.31040000915527344},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.30809998512268066},{"id":"https://openalex.org/C51323132","wikidata":"https://www.wikidata.org/wiki/Q626251","display_name":"High-throughput screening","level":2,"score":0.3009999990463257},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.29919999837875366},{"id":"https://openalex.org/C2776243700","wikidata":"https://www.wikidata.org/wiki/Q7252869","display_name":"Proximity ligation assay","level":3,"score":0.29670000076293945},{"id":"https://openalex.org/C59593255","wikidata":"https://www.wikidata.org/wiki/Q901663","display_name":"Molecular dynamics","level":2,"score":0.29249998927116394},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.27480000257492065},{"id":"https://openalex.org/C2776120743","wikidata":"https://www.wikidata.org/wiki/Q3271540","display_name":"Mechanism of action","level":3,"score":0.2621000111103058},{"id":"https://openalex.org/C2778707968","wikidata":"https://www.wikidata.org/wiki/Q417555","display_name":"Teniposide","level":4,"score":0.2567000091075897}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1038/s41598-026-79009-9","doi":"https://doi.org/10.1038/s41598-026-79009-9","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-79009-9","pdf_url":"https://www.nature.com/articles/s41598-026-79009-9_reference.pdf","source":{"id":"https://openalex.org/S196734849","display_name":"Scientific Reports","issn_l":"2045-2322","issn":["2045-2322"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Scientific Reports","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1038/s41598-026-79009-9","doi":"https://doi.org/10.1038/s41598-026-79009-9","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-79009-9","pdf_url":"https://www.nature.com/articles/s41598-026-79009-9_reference.pdf","source":{"id":"https://openalex.org/S196734849","display_name":"Scientific Reports","issn_l":"2045-2322","issn":["2045-2322"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Scientific Reports","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225793409.pdf","grobid_xml":"https://content.openalex.org/works/W7225793409.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Podophyllotoxin":[0],"(PTOX),":[1],"a":[2,43,88,122,127,133,143,163,185,202,214],"plant-derived":[3],"lignan":[4],"with":[5,17,111],"potent":[6],"anticancer":[7],"properties,":[8],"is":[9,77],"hypothesized":[10],"to":[11,51,126],"mimic":[12],"Smac":[13],"activity":[14],"by":[15],"interacting":[16],"Inhibitor":[18],"of":[19,61,104,136,177,205],"Apoptosis":[20],"Protein":[21],"(IAP)":[22],"BIR":[23],"domains.":[24],"However,":[25],"the":[26,53,58,74,84,93,102,118,148,154,175,178,191,206],"precise":[27],"molecular":[28],"mechanisms":[29],"governing":[30],"these":[31,171],"interactions":[32],"remain":[33],"poorly":[34],"understood.":[35],"In":[36],"this":[37,98,108],"study,":[38],"we":[39,100],"developed":[40],"and":[41,63,68,81,132,194],"validated":[42],"highly":[44],"sensitive,":[45,186],"cell-free":[46],"split-luciferase":[47],"complementation":[48],"assay":[49],"designed":[50],"quantify":[52],"real-time":[54,187],"interaction":[55,76],"dynamics":[56],"between":[57],"BIR2\u2013BIR3":[59],"domains":[60],"XIAP":[62],"its":[64,151,210],"key":[65],"targets,":[66],"caspase-3":[67],"caspase-9.":[69],"Our":[70],"results":[71],"demonstrate":[72],"that":[73,198],"BIR2\u2013BIR3\u2013NLuc/caspase-9-CLuc":[75],"significantly":[78],"more":[79,159],"robust":[80],"stable":[82],"than":[83],"BIR2\u2013BIR3\u2013NLuc/caspase-3-CLuc":[85],"interaction,":[86,150],"highlighting":[87],"preferential":[89],"binding":[90],"mechanism":[91],"at":[92],"initiator":[94],"caspase":[95],"level.":[96],"Utilizing":[97],"platform,":[99],"investigated":[101],"effects":[103],"PTOX":[105,116,141,199],"in":[106,112,121,130],"modulating":[107],"interaction.":[109],"Consistent":[110],"silico":[113],"docking":[114],"predictions,":[115],"disrupted":[117],"XIAP\u2013caspase-9":[119],"complex":[120],"concentration-dependent":[123],"manner,":[124],"leading":[125],"marked":[128],"reduction":[129],"luminescence":[131],"subsequent":[134],"restoration":[135],"caspase-9":[137,155],"enzymatic":[138],"activity.":[139],"While":[140],"showed":[142],"minor":[144],"inhibitory":[145],"effect":[146],"on":[147,153,170],"XIAP\u2013caspase-3":[149],"impact":[152,169],"axis":[156,193],"was":[157],"markedly":[158],"pronounced.":[160],"Furthermore,":[161],"Carboplatin,":[162],"DNA-crosslinking":[164],"agent,":[165],"exhibited":[166],"no":[167],"significant":[168],"protein-protein":[172],"interactions,":[173],"confirming":[174],"specificity":[176],"observed":[179],"PTOX-mediated":[180],"effects.":[181],"These":[182],"findings":[183],"establish":[184],"platform":[188],"for":[189],"monitoring":[190],"XIAP\u2013caspase":[192],"provide":[195],"compelling":[196],"evidence":[197],"acts":[200],"as":[201,213],"targeted":[203],"modulator":[204],"apoptotic":[207],"pathway,":[208],"warranting":[209],"further":[211],"development":[212],"pharmacological":[215],"agent.":[216]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}