{"id":"https://openalex.org/W7225617945","doi":"https://doi.org/10.21203/rs.3.rs-11450596/v1","title":"Mutation-dependent activity of BI4020, JND3229, and TQB3804 in an EGFR mutant Ba/F3 cell panel","display_name":"Mutation-dependent activity of BI4020, JND3229, and TQB3804 in an EGFR mutant Ba/F3 cell panel","publication_year":2026,"publication_date":"2026-11-09","ids":{"openalex":"https://openalex.org/W7225617945","doi":"https://doi.org/10.21203/rs.3.rs-11450596/v1"},"language":"en","primary_location":{"id":"doi:10.21203/rs.3.rs-11450596/v1","doi":"https://doi.org/10.21203/rs.3.rs-11450596/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11450596/v1","pdf_url":"https://www.researchsquare.com/article/rs-11450596/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.researchsquare.com/article/rs-11450596/latest.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5044606441","display_name":"Ayaka Mimura","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Ayaka Mimura","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063865769","display_name":"Nobuaki Ochi","orcid":"https://orcid.org/0000-0002-9043-1327","observed_orcids":["https://orcid.org/0000-0002-9043-1327"]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Nobuaki Ochi","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161333128","display_name":"Masami Takeyama","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Masami Takeyama","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047240476","display_name":"Yasunari Nagasaki","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yasunari Nagasaki","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108561232","display_name":"Tomoko Ikeda","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Tomoko Ikeda","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082617727","display_name":"Takuya Fukazawa","orcid":"https://orcid.org/0000-0003-2890-0599","observed_orcids":["https://orcid.org/0000-0003-2890-0599"]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takuya Fukazawa","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110132944","display_name":"Akio Hiraki","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Akio Hiraki","raw_affiliation_strings":["Okayama Suiseikai Hospital"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Okayama Suiseikai Hospital","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066700160","display_name":"Katsuyuki Kiura","orcid":"https://orcid.org/0000-0002-9172-9379","observed_orcids":["https://orcid.org/0000-0002-9172-9379"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Katsuyuki Kiura","raw_affiliation_strings":["Okayama Suiseikai Hospital"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Okayama Suiseikai Hospital","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101711494","display_name":"Hidekazu Nakanishi","orcid":"https://orcid.org/0000-0003-0399-6299","observed_orcids":["https://orcid.org/0000-0003-0399-6299"]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Hidekazu Nakanishi","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5051924591","display_name":"Hiromichi Yamane","orcid":"https://orcid.org/0000-0002-7550-5607","observed_orcids":["https://orcid.org/0000-0002-7550-5607"]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Hiromichi Yamane","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5001897650","display_name":"Nagio Takigawa","orcid":"https://orcid.org/0000-0002-3835-5128","observed_orcids":["https://orcid.org/0000-0002-3835-5128"]},"institutions":[{"id":"https://openalex.org/I189996419","display_name":"Kawasaki Medical School","ror":"https://ror.org/059z11218","country_code":"JP","type":"education","lineage":["https://openalex.org/I189996419"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Nagio Takigawa","raw_affiliation_strings":["Kawasaki Medical School"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kawasaki Medical School","institution_ids":["https://openalex.org/I189996419"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.000699999975040555,"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/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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"}}],"keywords":[{"id":"https://openalex.org/keywords/egfr-c797s-mutation","display_name":"C797S mutation","score":0.8989999890327454},{"id":"https://openalex.org/keywords/fourth-generation-egfr-inhibitors","display_name":"fourth-generation EGFR inhibitors","score":0.8980000019073486},{"id":"https://openalex.org/keywords/osimertinib","display_name":"osimertinib","score":0.9959999918937683},{"id":"https://openalex.org/keywords/egfr-t790m-mutation","display_name":"T790M mutation","score":0.7369999885559082},{"id":"https://openalex.org/keywords/egfr-l858r-mutation","display_name":"L858R mutation","score":0.8650000095367432},{"id":"https://openalex.org/keywords/egfr-activating-mutations","display_name":"EGFR activating mutations","score":0.6660000085830688},{"id":"https://openalex.org/keywords/akt-phosphorylation","display_name":"Akt phosphorylation","score":0.8700000047683716},{"id":"https://openalex.org/keywords/lung-cancer","display_name":"lung cancer","score":0.7379999756813049}],"concepts":[{"id":"https://openalex.org/C2777626846","wikidata":"https://www.wikidata.org/wiki/Q21506464","display_name":"Osimertinib","level":5,"score":0.9261999726295471},{"id":"https://openalex.org/C2777930144","wikidata":"https://www.wikidata.org/wiki/Q25100112","display_name":"T790M","level":5,"score":0.8306999802589417},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.6850000023841858},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.6841999888420105},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5579000115394592},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.555899977684021},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.5049999952316284},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.4999000132083893},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.48350000381469727},{"id":"https://openalex.org/C2780783641","wikidata":"https://www.wikidata.org/wiki/Q738686","display_name":"MTT assay","level":3,"score":0.4523000121116638},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.421999990940094},{"id":"https://openalex.org/C2777506169","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"EGFR inhibitors","level":4,"score":0.396699994802475},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.3952000141143799},{"id":"https://openalex.org/C53227056","wikidata":"https://www.wikidata.org/wiki/Q189152","display_name":"Viability assay","level":3,"score":0.39309999346733093},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.3617999851703644},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.35440000891685486},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.3434000015258789},{"id":"https://openalex.org/C2994294914","wikidata":"https://www.wikidata.org/wiki/Q1645075","display_name":"Acquired resistance","level":3,"score":0.3158000111579895},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.30320000648498535},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.30239999294281006},{"id":"https://openalex.org/C163565370","wikidata":"https://www.wikidata.org/wiki/Q4308623","display_name":"Mutation testing","level":4,"score":0.29980000853538513},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.296099990606308},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.28940001130104065},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.28769999742507935},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.28200000524520874},{"id":"https://openalex.org/C176944494","wikidata":"https://www.wikidata.org/wiki/Q1415380","display_name":"Point mutation","level":4,"score":0.28189998865127563},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.2669000029563904},{"id":"https://openalex.org/C16318435","wikidata":"https://www.wikidata.org/wiki/Q149299","display_name":"Mutagenesis","level":4,"score":0.25679999589920044},{"id":"https://openalex.org/C2909831755","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Proto-Oncogene Proteins c-akt","level":4,"score":0.25}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.21203/rs.3.rs-11450596/v1","doi":"https://doi.org/10.21203/rs.3.rs-11450596/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11450596/v1","pdf_url":"https://www.researchsquare.com/article/rs-11450596/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.21203/rs.3.rs-11450596/v1","doi":"https://doi.org/10.21203/rs.3.rs-11450596/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-11450596/v1","pdf_url":"https://www.researchsquare.com/article/rs-11450596/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9476000070571899}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320320912","display_name":"Ministry of Education, Culture, Sports, Science and Technology","ror":"https://ror.org/048rj2z13"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225617945.pdf","grobid_xml":"https://content.openalex.org/works/W7225617945.grobid-xml"},"referenced_works_count":13,"referenced_works":["https://openalex.org/W1546552389","https://openalex.org/W1908940658","https://openalex.org/W2114918609","https://openalex.org/W2770828094","https://openalex.org/W2897694508","https://openalex.org/W2953475087","https://openalex.org/W2989251275","https://openalex.org/W3150192782","https://openalex.org/W4318559602","https://openalex.org/W4392099139","https://openalex.org/W4393156309","https://openalex.org/W4400944089","https://openalex.org/W7220374179"],"related_works":["https://openalex.org/W7213883482","https://openalex.org/W4395678079","https://openalex.org/W2953475087","https://openalex.org/W4307909388","https://openalex.org/W4294941651","https://openalex.org/W4362594113","https://openalex.org/W4282925103","https://openalex.org/W7124306727","https://openalex.org/W4389241811","https://openalex.org/W4393092990"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"EGFR":[2,9,32,47,65,174,207],"C797S":[3,157],"impairs":[4],"the":[5,77,164,188,205],"activity":[6,29,199],"of":[7,63,146],"covalent":[8],"inhibitors.":[10,78],"Several":[11],"fourth-generation":[12,194],"inhibitors":[13,195],"have":[14],"been":[15],"developed,":[16],"but":[17,95],"comparisons":[18],"across":[19],"different":[20],"experimental":[21],"systems":[22],"do":[23],"not":[24],"adequately":[25],"define":[26],"their":[27],"relative":[28],"against":[30],"individual":[31],"genotypes.":[33],"Methods":[34],"Osimertinib,":[35],"BI4020,":[36,169],"JND3229,":[37,170],"and":[38,66,108,116,123,128,130,139,148,171,175],"TQB3804":[39,151,172],"were":[40,83,114],"evaluated":[41],"in":[42,71,86,98,156,163,178,217],"Ba/F3":[43],"cells":[44,73,87,99],"expressing":[45,88,100],"wild-type":[46],"or":[48,92],"nine":[49],"mutant":[50],"variants.":[51],"Cell":[52],"viability":[53],"was":[54,69],"assessed":[55],"by":[56],"an":[57],"MTT":[58],"assay":[59],"after":[60,74],"96":[61],"h":[62],"exposure.":[64],"AKT":[67,176],"phosphorylation":[68,177],"examined":[70],"L858R/C797S-expressing":[72],"treatment":[75],"with":[76,91,104,121],"Results":[79],"Osimertinib":[80],"IC\u2085\u2080":[81,112,144,154],"values":[82,113,145,155],"1.39\u20132.84":[84],"nM":[85,97,125,132],"activating":[89,101],"mutations":[90,102],"without":[93,167],"T790M,":[94],"419.42\u20131422.52":[96],"together":[103],"C797S.":[105],"In":[106,135],"19Del/T790M/C797S":[107],"L858R/T790M/C797S":[109],"cells,":[110,137,180],"BI4020":[111,138],"0.39":[115],"0.20":[117],"nM,":[118],"respectively,":[119],"compared":[120],"61.18":[122],"13.59":[124],"for":[126,133],"JND3229":[127,140],"3.85":[129],"3.42":[131],"TQB3804.":[134],"L858R/C797S":[136,179],"showed":[141,152,183],"similar":[142],"mean":[143],"1.40":[147],"1.49":[149],"nM.":[150],"lower":[153],"compound":[158],"mutants":[159],"containing":[160],"T790M":[161],"than":[162],"corresponding":[165],"models":[166,221],"T790M.":[168],"reduced":[173],"whereas":[181],"osimertinib":[182],"little":[184],"apparent":[185],"suppression":[186],"under":[187],"same":[189],"conditions.":[190],"Conclusions":[191],"The":[192],"three":[193],"exhibited":[196],"distinct":[197],"genotype-associated":[198],"profiles.":[200],"These":[201],"findings":[202],"support":[203],"evaluating":[204],"complete":[206],"mutation":[208],"profile":[209],"when":[210],"comparing":[211],"C797S-active":[212],"inhibitors,":[213],"while":[214],"further":[215],"validation":[216],"human":[218],"lung":[219],"cancer":[220],"is":[222],"required.":[223]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-10T00:00:00"}