{"id":"https://openalex.org/W7223138103","doi":"https://doi.org/10.26434/chemrxiv.15010755/v1","title":"Discovery of Nanomolar CDK2 Inhibitors Using Boltz-2","display_name":"Discovery of Nanomolar CDK2 Inhibitors Using Boltz-2","publication_year":2026,"publication_date":"2026-10-21","ids":{"openalex":"https://openalex.org/W7223138103","doi":"https://doi.org/10.26434/chemrxiv.15010755/v1"},"language":"en","primary_location":{"id":"doi:10.26434/chemrxiv.15010755/v1","doi":"https://doi.org/10.26434/chemrxiv.15010755/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010755/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010755/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"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://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010755/v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5048156327","display_name":"Sven M. Papidocha","orcid":"https://orcid.org/0009-0000-6375-5185","observed_orcids":["https://orcid.org/0009-0000-6375-5185"]},"institutions":[{"id":"https://openalex.org/I185261750","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087","country_code":"CA","type":"education","lineage":["https://openalex.org/I185261750"]},{"id":"https://openalex.org/I4210127509","display_name":"Vector Institute","ror":"https://ror.org/03kqdja62","country_code":"CA","type":"facility","lineage":["https://openalex.org/I4210127509"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Sven M. Papidocha","raw_affiliation_strings":["Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6","Vector Institute for Artificial Intelligence, W1140-108 College St., Toronto, ON, Canada, M5G 0C6"],"raw_orcid":"https://orcid.org/0009-0000-6375-5185","affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6","institution_ids":["https://openalex.org/I185261750"]},{"raw_affiliation_string":"Vector Institute for Artificial Intelligence, W1140-108 College St., Toronto, ON, Canada, M5G 0C6","institution_ids":["https://openalex.org/I4210127509"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159034715","display_name":"Yoshihiro Ogura","orcid":"https://orcid.org/0009-0002-5079-9319","observed_orcids":["https://orcid.org/0009-0002-5079-9319"]},"institutions":[{"id":"https://openalex.org/I185261750","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087","country_code":"CA","type":"education","lineage":["https://openalex.org/I185261750"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Yoshihiro Ogura","raw_affiliation_strings":["Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6"],"raw_orcid":"https://orcid.org/0009-0002-5079-9319","affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6","institution_ids":["https://openalex.org/I185261750"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5124511572","display_name":"Jiahe Ren","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I185261750","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087","country_code":"CA","type":"education","lineage":["https://openalex.org/I185261750"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Jiahe Ren","raw_affiliation_strings":["Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6","institution_ids":["https://openalex.org/I185261750"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159041352","display_name":"Mikhail Saykin","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I185261750","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087","country_code":"CA","type":"education","lineage":["https://openalex.org/I185261750"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Mikhail Saykin","raw_affiliation_strings":["Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6","institution_ids":["https://openalex.org/I185261750"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069099185","display_name":"Stuart R. Green","orcid":"https://orcid.org/0000-0002-2960-9683","observed_orcids":["https://orcid.org/0000-0002-2960-9683"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Stuart Green","raw_affiliation_strings":["Acceleration Consortium, 700 University Ave., Toronto, ON, Canada, M7A 2S4"],"raw_orcid":"https://orcid.org/0000-0002-2960-9683","affiliations":[{"raw_affiliation_string":"Acceleration Consortium, 700 University Ave., Toronto, ON, Canada, M7A 2S4","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044494119","display_name":"Varinia Bernales","orcid":"https://orcid.org/0000-0002-8446-7956","observed_orcids":["https://orcid.org/0000-0002-8446-7956"]},"institutions":[{"id":"https://openalex.org/I185261750","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087","country_code":"CA","type":"education","lineage":["https://openalex.org/I185261750"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Varinia Bernales","raw_affiliation_strings":["Department of Computer Science, University of Toronto, 40 St. George St., Toronto, ON, Canada, M5S 2E4"],"raw_orcid":"https://orcid.org/0000-0002-8446-7956","affiliations":[{"raw_affiliation_string":"Department of Computer Science, University of Toronto, 40 St. George St., Toronto, ON, Canada, M5S 2E4","institution_ids":["https://openalex.org/I185261750"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5071495561","display_name":"Al\u00e1n Aspuru\u2010Guzik","orcid":"https://orcid.org/0000-0002-8277-4434","observed_orcids":["https://orcid.org/0000-0002-8277-4434"]},"institutions":[{"id":"https://openalex.org/I109736498","display_name":"Canadian Institute for Advanced Research","ror":"https://ror.org/01sdtdd95","country_code":"CA","type":"facility","lineage":["https://openalex.org/I109736498"]},{"id":"https://openalex.org/I185261750","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087","country_code":"CA","type":"education","lineage":["https://openalex.org/I185261750"]},{"id":"https://openalex.org/I4210127509","display_name":"Vector Institute","ror":"https://ror.org/03kqdja62","country_code":"CA","type":"facility","lineage":["https://openalex.org/I4210127509"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Al\u00e1n Aspuru-Guzik","raw_affiliation_strings":["Acceleration Consortium, 700 University Ave., Toronto, ON, Canada, M7A 2S4","Canadian Institute for Advanced Research (CIFAR), 661 University Ave., Toronto, ON, Canada, M5G 1M1","Department of Chemical Engineering & Applied Chemistry, University of Toronto, 200 College St., Toronto, ON, M5S 3E5","Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6","Department of Computer Science, University of Toronto, 40 St. George St., Toronto, ON, Canada, M5S 2E4","Department of Materials Science & Engineering, University of Toronto, 184 College St., Toronto, ON, M5S 3E4","Institute of Medical Science, University of Toronto, 1 King\u2019s College Circle, Toronto, ON, M5S 1A8","NVIDIA, 431 King St. W #6th, Toronto, ON, M5V 1K4","Vector Institute for Artificial Intelligence, W1140-108 College St., Toronto, ON, Canada, M5G 0C6"],"raw_orcid":"https://orcid.org/0000-0002-8277-4434","affiliations":[{"raw_affiliation_string":"Acceleration Consortium, 700 University Ave., Toronto, ON, Canada, M7A 2S4","institution_ids":[]},{"raw_affiliation_string":"Canadian Institute for Advanced Research (CIFAR), 661 University Ave., Toronto, ON, Canada, M5G 1M1","institution_ids":["https://openalex.org/I109736498"]},{"raw_affiliation_string":"Department of Chemical Engineering & Applied Chemistry, University of Toronto, 200 College St., Toronto, ON, M5S 3E5","institution_ids":["https://openalex.org/I185261750"]},{"raw_affiliation_string":"Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, Canada, M5S 3H6","institution_ids":["https://openalex.org/I185261750"]},{"raw_affiliation_string":"Department of Computer Science, University of Toronto, 40 St. George St., Toronto, ON, Canada, M5S 2E4","institution_ids":["https://openalex.org/I185261750"]},{"raw_affiliation_string":"Department of Materials Science & Engineering, University of Toronto, 184 College St., Toronto, ON, M5S 3E4","institution_ids":["https://openalex.org/I185261750"]},{"raw_affiliation_string":"Institute of Medical Science, University of Toronto, 1 King\u2019s College Circle, Toronto, ON, M5S 1A8","institution_ids":["https://openalex.org/I185261750"]},{"raw_affiliation_string":"NVIDIA, 431 King St. W #6th, Toronto, ON, M5V 1K4","institution_ids":[]},{"raw_affiliation_string":"Vector Institute for Artificial Intelligence, W1140-108 College St., Toronto, ON, Canada, M5G 0C6","institution_ids":["https://openalex.org/I4210127509"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.9994999766349792,"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":0.9994999766349792,"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/T14099","display_name":"Synthesis and Characterization of Heterocyclic Compounds","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/cdk2-inhibitors","display_name":"CDK2 inhibitors","score":0.9480000138282776},{"id":"https://openalex.org/keywords/boltz-2","display_name":"Boltz-2","score":0.9670000076293945},{"id":"https://openalex.org/keywords/virtual-screening","display_name":"virtual screening","score":0.9089999794960022},{"id":"https://openalex.org/keywords/tetrahydroquinolines","display_name":"tetrahydroquinolines","score":0.9750000238418579},{"id":"https://openalex.org/keywords/multicomponent-synthesis","display_name":"multicomponent synthesis","score":0.8989999890327454},{"id":"https://openalex.org/keywords/hit-identification","display_name":"hit identification","score":0.7910000085830688},{"id":"https://openalex.org/keywords/hit-optimization","display_name":"hit optimization","score":0.9300000071525574},{"id":"https://openalex.org/keywords/nanomolar-inhibitors","display_name":"nanomolar inhibitors","score":0.6840000152587891}],"concepts":[{"id":"https://openalex.org/C103697762","wikidata":"https://www.wikidata.org/wiki/Q4112105","display_name":"Virtual screening","level":3,"score":0.7746999859809875},{"id":"https://openalex.org/C99726746","wikidata":"https://www.wikidata.org/wiki/Q906396","display_name":"Chemical space","level":3,"score":0.6126999855041504},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5889000296592712},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.57669997215271},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5756999850273132},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.5062999725341797},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.4912000000476837},{"id":"https://openalex.org/C51323132","wikidata":"https://www.wikidata.org/wiki/Q626251","display_name":"High-throughput screening","level":2,"score":0.4577000141143799},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.4142000079154968},{"id":"https://openalex.org/C157764524","wikidata":"https://www.wikidata.org/wiki/Q1383412","display_name":"Throughput","level":3,"score":0.39089998602867126},{"id":"https://openalex.org/C171250308","wikidata":"https://www.wikidata.org/wiki/Q11468","display_name":"Nanotechnology","level":1,"score":0.34950000047683716},{"id":"https://openalex.org/C174348530","wikidata":"https://www.wikidata.org/wiki/Q188635","display_name":"Bridging (networking)","level":2,"score":0.3465999960899353},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.3407000005245209},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3188999891281128},{"id":"https://openalex.org/C171852809","wikidata":"https://www.wikidata.org/wiki/Q731154","display_name":"Chemical biology","level":2,"score":0.29750001430511475},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.27129998803138733},{"id":"https://openalex.org/C3018795828","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Binding affinities","level":3,"score":0.25600001215934753},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.2524000108242035},{"id":"https://openalex.org/C85196483","wikidata":"https://www.wikidata.org/wiki/Q6545857","display_name":"Ligand binding assay","level":3,"score":0.250900000333786}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.26434/chemrxiv.15010755/v1","doi":"https://doi.org/10.26434/chemrxiv.15010755/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010755/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010755/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.26434/chemrxiv.15010755/v1","doi":"https://doi.org/10.26434/chemrxiv.15010755/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010755/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010755/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G397280496","display_name":null,"funder_award_id":"2022-00042","funder_id":"https://openalex.org/F4320326644","funder_display_name":"Canada First Research Excellence Fund"},{"id":"https://openalex.org/G6168044780","display_name":null,"funder_award_id":"CFREF-2022-00042","funder_id":"https://openalex.org/F4320322015","funder_display_name":"University of Toronto"},{"id":"https://openalex.org/G8375293472","display_name":"Acceleration Consortium: Self-Driving Labs for Molecular and Materials Discovery","funder_award_id":"CFREF-2022-00042","funder_id":"https://openalex.org/F4320326644","funder_display_name":"Canada First Research Excellence Fund"}],"funders":[{"id":"https://openalex.org/F4320320924","display_name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","ror":"https://ror.org/00yjd3n13"},{"id":"https://openalex.org/F4320322015","display_name":"University of Toronto","ror":"https://ror.org/03dbr7087"},{"id":"https://openalex.org/F4320326644","display_name":"Canada First Research Excellence Fund","ror":"https://ror.org/01ktx4s83"},{"id":"https://openalex.org/F4320334593","display_name":"Natural Sciences and Engineering Research Council of Canada","ror":"https://ror.org/01h531d29"},{"id":"https://openalex.org/F4320338262","display_name":"Daiichi Sankyo Europe","ror":"https://ror.org/01qhj1g70"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7223138103.pdf","grobid_xml":"https://content.openalex.org/works/W7223138103.grobid-xml"},"referenced_works_count":8,"referenced_works":["https://openalex.org/W4404565424","https://openalex.org/W4411463597","https://openalex.org/W4414088430","https://openalex.org/W4417145370","https://openalex.org/W7117475843","https://openalex.org/W7167470268","https://openalex.org/W7172444685","https://openalex.org/W7222975828"],"related_works":["https://openalex.org/W3013022884","https://openalex.org/W7161155075","https://openalex.org/W2990391624","https://openalex.org/W7130370595","https://openalex.org/W1996352794","https://openalex.org/W7204594495","https://openalex.org/W7212396947","https://openalex.org/W7167470268","https://openalex.org/W2951017457","https://openalex.org/W2774408741"],"abstract_inverted_index":{"The":[0],"computational":[1],"design":[2],"of":[3,91,111,123],"small-molecule":[4],"ligands":[5],"for":[6,33],"pharmaceutical":[7],"targets":[8],"has":[9],"historically":[10],"been":[11,55],"hindered":[12],"by":[13],"a":[14,76,87,98],"strict":[15],"trade-off":[16],"between":[17],"screening":[18,89,110],"throughput":[19],"and":[20,115],"predictive":[21],"accuracy.":[22],"While":[23],"next-generation":[24],"cofolding":[25],"affinity":[26,84],"models":[27,53],"like":[28],"Boltz-2":[29,102],"hold":[30],"immense":[31],"promise":[32],"bridging":[34],"this":[35],"gap,":[36],"their":[37,63],"utility":[38],"in":[39],"prospective":[40],"medicinal":[41],"chemistry":[42],"campaigns":[43],"remains":[44],"largely":[45],"unexplored.":[46],"To":[47],"date,":[48],"virtual":[49,109],"screens":[50],"leveraging":[51],"these":[52,112],"have":[54],"overwhelmingly":[56],"restricted":[57],"to":[58,65],"standard":[59],"commercial":[60],"catalogs,":[61],"leaving":[62],"capacity":[64],"navigate":[66],"novel,":[67],"synthetically":[68],"tailored":[69],"chemical":[70],"spaces":[71],"unevaluated.":[72],"Here,":[73],"we":[74],"present":[75],"novel":[77],"hit":[78,117],"discovery":[79],"platform":[80],"that":[81],"integrates":[82],"Boltz-2\u2019s":[83],"module":[85],"with":[86],"custom":[88],"space":[90],"stereochemically":[92],"complex":[93],"tetrahydroquinolines,":[94],"accessed":[95],"efficiently":[96],"via":[97],"single-step":[99],"multicomponent":[100],"approach.":[101],"successfully":[103],"guided":[104],"both":[105],"the":[106],"initial":[107],"high-throughput":[108],"targeted":[113],"scaffolds":[114],"subsequent":[116],"optimization,":[118],"rapidly":[119],"yielding":[120],"nanomolar":[121],"inhibitors":[122],"cyclin-dependent":[124],"kinase":[125],"2":[126],"(CDK2).":[127]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2026-10-22T00:00:00"}