{"id":"https://openalex.org/W7225815439","doi":"https://doi.org/10.1038/s41598-026-78012-4","title":"Integrated multi-omics prioritizes small-molecule candidates for the N-cadherin HAV site and reveals endpoint-level toxicity trade-offs","display_name":"Integrated multi-omics prioritizes small-molecule candidates for the N-cadherin HAV site and reveals endpoint-level toxicity trade-offs","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225815439","doi":"https://doi.org/10.1038/s41598-026-78012-4"},"language":"en","primary_location":{"id":"doi:10.1038/s41598-026-78012-4","doi":"https://doi.org/10.1038/s41598-026-78012-4","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-78012-4","pdf_url":null,"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","license_id":"https://openalex.org/licenses/cc-by","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://doi.org/10.1038/s41598-026-78012-4","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5080555059","display_name":"Mohsen Sisakht","orcid":"https://orcid.org/0000-0002-9882-7211","observed_orcids":["https://orcid.org/0000-0002-9882-7211"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mohsen Sisakht","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022347123","display_name":"Jafar Fallahi","orcid":"https://orcid.org/0000-0002-8485-9247","observed_orcids":["https://orcid.org/0000-0002-8485-9247"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jafar Fallahi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161423442","display_name":"Vahab Alamdari-Palang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Vahab Alamdari-Palang","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060322538","display_name":"Vahid Razban","orcid":"https://orcid.org/0000-0002-8966-6081","observed_orcids":["https://orcid.org/0000-0002-8966-6081"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Vahid Razban","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5139543023","display_name":"Mohammad Hassani","orcid":"https://orcid.org/0000-0002-8671-5191","observed_orcids":["https://orcid.org/0000-0002-8671-5191"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mohammad Hassani","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5027005024","display_name":"Mahmoud Hassani","orcid":"https://orcid.org/0000-0002-3142-8320","observed_orcids":["https://orcid.org/0000-0002-3142-8320"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Mahmoud Hassani","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5007247894","display_name":"Sahar Khajeh","orcid":"https://orcid.org/0000-0003-1614-2962","observed_orcids":["https://orcid.org/0000-0003-1614-2962"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sahar Khajeh","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":2690,"currency":"USD","value_usd":2690},"apc_paid":{"value":2690,"currency":"USD","value_usd":2690},"fwci":0.0,"has_fulltext":false,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.9932000041007996,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9932000041007996,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10336","display_name":"Cancer Cells and Metastasis","score":0.00279999990016222,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T10831","display_name":"Cell Adhesion Molecules Research","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/2723","display_name":"Immunology and Allergy"},"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/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.7630000114440918},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.507099986076355},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4553000032901764},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.390500009059906},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.33059999346733093},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.32499998807907104},{"id":"https://openalex.org/C51785407","wikidata":"https://www.wikidata.org/wiki/Q2627568","display_name":"Effector","level":2,"score":0.3127000033855438},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.29429998993873596},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.2809999883174896},{"id":"https://openalex.org/C164126121","wikidata":"https://www.wikidata.org/wiki/Q766383","display_name":"Quantitative structure\u2013activity relationship","level":2,"score":0.2736000120639801},{"id":"https://openalex.org/C33070731","wikidata":"https://www.wikidata.org/wiki/Q7218","display_name":"Toxicology","level":1,"score":0.2621000111103058},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2614000141620636},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.2526000142097473},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.25200000405311584},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.2513999938964844},{"id":"https://openalex.org/C3020225094","wikidata":"https://www.wikidata.org/wiki/Q80091","display_name":"Area under curve","level":3,"score":0.250900000333786}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1038/s41598-026-78012-4","doi":"https://doi.org/10.1038/s41598-026-78012-4","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-78012-4","pdf_url":null,"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","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Scientific Reports","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1038/s41598-026-78012-4","doi":"https://doi.org/10.1038/s41598-026-78012-4","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41598-026-78012-4","pdf_url":null,"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","license_id":"https://openalex.org/licenses/cc-by","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":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Abstract":[0],"N-cadherin":[1,25,54,101,463],"(CDH2)":[2],"is":[3],"a":[4,27,108,119,129,189,231,292,377,453],"central":[5],"effector":[6],"of":[7,32,81,209,234,244,287,296,304,307,311,344,356,363,373,382,446],"epithelial-to-mesenchymal":[8],"transition":[9],"(EMT)":[10],"that":[11,44],"contributes":[12],"to":[13,40,99,200,399,486,491],"invasion,":[14],"metastasis":[15],"and":[16,21,66,84,93,105,159,161,176,186,207,242,267,290,309,318,330,350,361,429,450,467,482],"therapy":[17],"resistance.":[18],"Although":[19],"peptide":[20],"antibody":[22],"approaches":[23],"validate":[24],"as":[26,140,321,434],"therapeutic":[28],"target,":[29],"small-molecule":[30],"modulators":[31,419],"its":[33],"adhesive":[34],"interface":[35],"remain":[36],"limited.":[37],"We":[38],"aimed":[39],"prioritize":[41],"candidate":[42,417],"compounds":[43,88,211],"suppress":[45],"EMT-associated":[46],"transcriptional":[47],"programs,":[48],"show":[49],"plausible":[50],"binding":[51,216],"at":[52,217,222,313],"the":[53,59,100,141,218,223,273,322,326,331,345,357,367,400,435,447,468],"HAV":[55,103,219],"(His79-Ala80-Val81)":[56],"hotspot,":[57],"preserve":[58],"biomass":[60],"objective":[61],"in":[62,359],"context-specific":[63],"metabolic":[64,150,430],"models,":[65],"minimize":[67],"predicted":[68,143,215,469],"endpoint-level":[69,333],"toxicity":[70,133,228],"liabilities.":[71],"LINCS":[72],"L1000":[73],"level-5":[74],"profiles":[75],"were":[76,97,152,183],"screened":[77],"for":[78],"concordant":[79,285],"down-regulation":[80],"CDH2,":[82,288],"SNAI1":[83,289],"SNAI2,":[85,291],"yielding":[86],"20":[87,210],"across":[89,146],"cell":[90],"lines,":[91],"doses":[92],"exposure":[94],"times.":[95],"Compounds":[96],"docked":[98],"EC1":[102,112],"pocket":[104,220],"compared":[106],"with":[107,128,154,325,348,439],"spatially":[109],"separated":[110],"non-HAV":[111,224],"control":[113,225],"surface.":[114,226],"Toxicity":[115],"was":[116,135,257,261,265,269,319,397],"evaluated":[117],"using":[118,137,156,163,188],"multi-task":[120],"DeepChem":[121],"Graph":[122],"Convolutional":[123],"Network":[124],"trained":[125],"on":[126],"Tox21":[127],"scaffold-based":[130],"split.":[131],"Predicted":[132],"risk":[134],"summarized":[136,162],"max-risk,":[138],"defined":[139],"highest":[142],"positive-class":[144],"probability":[145],"12":[147],"endpoints.":[148],"Context-specific":[149],"effects":[151],"modeled":[153,253],"Human1":[155],"E-Flux,":[157],"pFBA":[158],"FVA,":[160],"Objective":[164],"Preservation":[165],"Ratio":[166],"(OPR),":[167],"Metabolic":[168],"Impact":[169],"Score":[170,179],"(MIS),":[171],"Targeted":[172],"Pathway":[173],"Selectivity":[174],"(TPS),":[175],"Homeostasis":[177],"Disruption":[178],"(HDS).":[180],"Evidence":[181],"pillars":[182],"winsorized,":[184],"normalized":[185],"integrated":[187],"transparent":[190],"weighted":[191],"composite":[192],"score.":[193],"Docking":[194],"energies":[195],"ranged":[196],"from":[197,480],"\u2212":[198,201,297,383],"8.1":[199],"5.9":[202],"kcal":[203,299,387,409],"mol":[204,300,388,410],"\u20131":[205,301,411],",":[206,302,391],"19":[208],"showed":[212,284,340],"more":[213],"favorable":[214,378,454],"than":[221],"The":[227,475],"model":[229],"achieved":[230],"micro-averaged":[232],"ROC-AUC":[233],"0.775":[235],"(bootstrap":[236,246],"95%":[237,247],"CI":[238,248],"0.756":[239],"\u2013":[240,250,389,405],"0.794)":[241],"PR-AUC":[243],"0.335":[245],"0.298":[249],"0.374).":[251],"Across":[252],"conditions,":[254],"median":[255,259,263],"OPR":[256,303],"1.12,":[258],"TPS":[260,306],"0.165,":[262],"MIS":[264],"0.79,":[266],"HDS":[268],"uniformly":[270],"low.":[271],"Under":[272],"conservative":[274],"max-risk-based":[275],"integration,":[276],"BRD.K09587429":[277,432],"ranked":[278,316],"first":[279],"(composite":[280],"score":[281,295,329],"0.656).":[282],"It":[283],"suppression":[286],"HAV-site":[293,346,425,448],"docking":[294,328],"6.7":[298],"1.081,":[305],"0.184,":[308],"max-risk":[310],"0.554":[312],"SR-ARE.":[314],"BRD.K04021425":[315],"second":[317],"retained":[320],"alternative":[323],"candidate,":[324,438],"strongest":[327],"lowest":[332],"max-risk.":[334],"A":[335],"100-ns":[336],"molecular":[337,440,465],"dynamics":[338,441],"simulation":[339],"persistent":[341,443],"computational":[342,444],"occupancy":[343,445],"region,":[347],"His79":[349],"Ala80":[351],"remaining":[352],"within":[353],"0.4":[354],"nm":[355],"ligand":[358],"96.9%":[360],"99.1%":[362],"frames,":[364],"respectively,":[365],"over":[366],"20\u2013100":[368],"ns":[369,403],"interval.":[370],"MM-PBSA":[371,451],"analysis":[372,396],"81":[374],"snapshots":[375],"yielded":[376],"end-state":[379,456],"binding-energy":[380],"estimate":[381],"24.58":[384],"\u00b1":[385,407],"6.90":[386],"1":[390],"which":[392],"remained":[393],"consistent":[394],"when":[395],"restricted":[398],"final":[401],"50":[402],"(":[404],"27.22":[406],"5.68":[408],").":[412],"This":[413],"multi-omics":[414],"framework":[415,476],"prioritizes":[416],"N-cadherin/EMT":[418],"by":[420],"jointly":[421],"considering":[422],"transcriptomic":[423],"directionality,":[424],"docking,":[426],"endpoint-resolved":[427],"toxicity,":[428],"selectivity.":[431],"emerged":[433],"highest-ranked":[436],"discovery-stage":[437],"showing":[442],"region":[449],"indicating":[452],"model-dependent":[455],"energetic":[457],"profile;":[458],"however,":[459],"direct":[460],"binding,":[461],"functional":[462],"antagonism,":[464],"mechanism,":[466],"SR-ARE-associated":[470],"liability":[471],"require":[472],"experimental":[473],"validation.":[474],"distinguishes":[477],"structural":[478],"plausibility":[479],"safety":[481],"can":[483],"be":[484],"adapted":[485],"other":[487],"protein-protein":[488],"interfaces":[489],"relevant":[490],"metastatic":[492],"cancer":[493],"biology.":[494]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}
