{"id":"https://openalex.org/W4410231349","doi":"https://doi.org/10.1021/acs.jcim.5c00107","title":"Integrating Pharmacokinetics and Quantitative Systems Pharmacology Approaches in Generative Drug Design","display_name":"Integrating Pharmacokinetics and Quantitative Systems Pharmacology Approaches in Generative Drug Design","publication_year":2025,"publication_date":"2025-05-09","ids":{"openalex":"https://openalex.org/W4410231349","doi":"https://doi.org/10.1021/acs.jcim.5c00107","pmid":"https://pubmed.ncbi.nlm.nih.gov/40343729"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.5c00107","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00107","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1021/acs.jcim.5c00107","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5052982318","display_name":"Helle W. van den Maagdenberg","orcid":"https://orcid.org/0000-0002-9718-7806"},"institutions":[{"id":"https://openalex.org/I4210133171","display_name":"Centre for Human Drug Research","ror":"https://ror.org/044hshx49","country_code":"NL","type":"facility","lineage":["https://openalex.org/I4210133171"]},{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Helle W. van den Maagdenberg","raw_affiliation_strings":["Leiden Academic Centre of Drug Research","Leiden University"],"affiliations":[{"raw_affiliation_string":"Leiden Academic Centre of Drug Research","institution_ids":["https://openalex.org/I4210133171"]},{"raw_affiliation_string":"Leiden University","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5115951664","display_name":"Jikke de Mol van Otterloo","orcid":null},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]},{"id":"https://openalex.org/I4210133171","display_name":"Centre for Human Drug Research","ror":"https://ror.org/044hshx49","country_code":"NL","type":"facility","lineage":["https://openalex.org/I4210133171"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Jikke de Mol van Otterloo","raw_affiliation_strings":["Leiden Academic Centre of Drug Research","Leiden University"],"affiliations":[{"raw_affiliation_string":"Leiden Academic Centre of Drug Research","institution_ids":["https://openalex.org/I4210133171"]},{"raw_affiliation_string":"Leiden University","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049073682","display_name":"J. G. Coen van Hasselt","orcid":"https://orcid.org/0000-0002-1664-7314"},"institutions":[{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]},{"id":"https://openalex.org/I4210133171","display_name":"Centre for Human Drug Research","ror":"https://ror.org/044hshx49","country_code":"NL","type":"facility","lineage":["https://openalex.org/I4210133171"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"J. G. Coen van Hasselt","raw_affiliation_strings":["Leiden Academic Centre of Drug Research","Leiden University"],"affiliations":[{"raw_affiliation_string":"Leiden Academic Centre of Drug Research","institution_ids":["https://openalex.org/I4210133171"]},{"raw_affiliation_string":"Leiden University","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077172862","display_name":"Piet H. van der Graaf","orcid":"https://orcid.org/0000-0003-1314-3484"},"institutions":[{"id":"https://openalex.org/I4210092647","display_name":"Research and Studies Telecommunications Centre","ror":"https://ror.org/00ga0xw04","country_code":"TN","type":"facility","lineage":["https://openalex.org/I4210092647"]},{"id":"https://openalex.org/I4210119960","display_name":"Certara (United States)","ror":"https://ror.org/02kxjqp24","country_code":"US","type":"company","lineage":["https://openalex.org/I4210119960"]},{"id":"https://openalex.org/I4210133171","display_name":"Centre for Human Drug Research","ror":"https://ror.org/044hshx49","country_code":"NL","type":"facility","lineage":["https://openalex.org/I4210133171"]},{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL","TN","US"],"is_corresponding":false,"raw_author_name":"Piet H. van der Graaf","raw_affiliation_strings":["Certara","Leiden Academic Centre of Drug Research","Leiden University"],"affiliations":[{"raw_affiliation_string":"Certara","institution_ids":["https://openalex.org/I4210092647","https://openalex.org/I4210119960"]},{"raw_affiliation_string":"Leiden Academic Centre of Drug Research","institution_ids":["https://openalex.org/I4210133171"]},{"raw_affiliation_string":"Leiden University","institution_ids":["https://openalex.org/I121797337"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5088996741","display_name":"Gerard J. P. van Westen","orcid":"https://orcid.org/0000-0003-0717-1817"},"institutions":[{"id":"https://openalex.org/I4210133171","display_name":"Centre for Human Drug Research","ror":"https://ror.org/044hshx49","country_code":"NL","type":"facility","lineage":["https://openalex.org/I4210133171"]},{"id":"https://openalex.org/I121797337","display_name":"Leiden University","ror":"https://ror.org/027bh9e22","country_code":"NL","type":"education","lineage":["https://openalex.org/I121797337"]}],"countries":["NL"],"is_corresponding":true,"raw_author_name":"Gerard J. P. van Westen","raw_affiliation_strings":["Leiden Academic Centre of Drug Research","Leiden University"],"affiliations":[{"raw_affiliation_string":"Leiden Academic Centre of Drug Research","institution_ids":["https://openalex.org/I4210133171"]},{"raw_affiliation_string":"Leiden University","institution_ids":["https://openalex.org/I121797337"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5088996741"],"corresponding_institution_ids":["https://openalex.org/I121797337","https://openalex.org/I4210133171"],"apc_list":null,"apc_paid":null,"fwci":8.3267,"has_fulltext":true,"cited_by_count":5,"citation_normalized_percentile":{"value":0.97570402,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":98},"biblio":{"volume":"65","issue":"10","first_page":"4783","last_page":"4796"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10621","display_name":"Gene Regulatory Network Analysis","score":0.9810000061988831,"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/T11407","display_name":"Innovative Microfluidic and Catalytic Techniques Innovation","score":0.9749000072479248,"subfield":{"id":"https://openalex.org/subfields/2204","display_name":"Biomedical Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"Pharmacokinetics","score":0.7152406573295593},{"id":"https://openalex.org/keywords/drug","display_name":"Drug","score":0.6555474996566772},{"id":"https://openalex.org/keywords/pharmacology","display_name":"Pharmacology","score":0.6293157339096069},{"id":"https://openalex.org/keywords/systems-pharmacology","display_name":"Systems pharmacology","score":0.46577781438827515},{"id":"https://openalex.org/keywords/clinical-pharmacology","display_name":"Clinical pharmacology","score":0.46099546551704407},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.37216177582740784},{"id":"https://openalex.org/keywords/medicine","display_name":"Medicine","score":0.3423733115196228},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.3403325080871582},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.11866036057472229}],"concepts":[{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.7152406573295593},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.6555474996566772},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6293157339096069},{"id":"https://openalex.org/C2779446555","wikidata":"https://www.wikidata.org/wiki/Q7663877","display_name":"Systems pharmacology","level":3,"score":0.46577781438827515},{"id":"https://openalex.org/C63433958","wikidata":"https://www.wikidata.org/wiki/Q1774688","display_name":"Clinical pharmacology","level":2,"score":0.46099546551704407},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.37216177582740784},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3423733115196228},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3403325080871582},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.11866036057472229}],"mesh":[{"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":"D010599","descriptor_name":"Pharmacokinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D010599","descriptor_name":"Pharmacokinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D010599","descriptor_name":"Pharmacokinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D021281","descriptor_name":"Quantitative Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D021281","descriptor_name":"Quantitative Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D021281","descriptor_name":"Quantitative Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D043705","descriptor_name":"Receptor, Adenosine A2A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D043705","descriptor_name":"Receptor, Adenosine A2A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D043705","descriptor_name":"Receptor, Adenosine A2A","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1021/acs.jcim.5c00107","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00107","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:40343729","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40343729","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,"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":"Journal of chemical information and modeling","raw_type":null},{"id":"pmh:oai:scholarlypublications.universiteitleiden.nl:item_4249656","is_oa":true,"landing_page_url":"https://hdl.handle.net/1887/4249656","pdf_url":"https://scholarlypublications.universiteitleiden.nl/access/item%3A4249657/view","source":{"id":"https://openalex.org/S4306400850","display_name":"Leiden Repository (Leiden University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I121797337","host_organization_name":"Leiden University","host_organization_lineage":["https://openalex.org/I121797337"],"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":"Journal of Chemical Information and Modeling","raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:12117666","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12117666","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"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":"J Chem Inf Model","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1021/acs.jcim.5c00107","is_oa":true,"landing_page_url":"https://doi.org/10.1021/acs.jcim.5c00107","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":49,"referenced_works":["https://openalex.org/W1977059612","https://openalex.org/W2055353351","https://openalex.org/W2059847559","https://openalex.org/W2122138332","https://openalex.org/W2151971404","https://openalex.org/W2156665896","https://openalex.org/W2160592148","https://openalex.org/W2329862012","https://openalex.org/W2529996553","https://openalex.org/W2740946158","https://openalex.org/W2786672974","https://openalex.org/W2892846700","https://openalex.org/W2944466104","https://openalex.org/W2966357564","https://openalex.org/W2968219050","https://openalex.org/W2971690404","https://openalex.org/W2973456138","https://openalex.org/W3034225747","https://openalex.org/W3082081167","https://openalex.org/W3083191400","https://openalex.org/W3093152954","https://openalex.org/W3123775255","https://openalex.org/W3125566655","https://openalex.org/W3127493072","https://openalex.org/W3134422943","https://openalex.org/W3136305460","https://openalex.org/W3158535672","https://openalex.org/W3211668464","https://openalex.org/W4225273113","https://openalex.org/W4225637038","https://openalex.org/W4239082087","https://openalex.org/W4292616203","https://openalex.org/W4304187519","https://openalex.org/W4307887810","https://openalex.org/W4313597804","https://openalex.org/W4379376560","https://openalex.org/W4380357668","https://openalex.org/W4391130256","https://openalex.org/W4391308260","https://openalex.org/W4391618201","https://openalex.org/W4392093325","https://openalex.org/W4392450309","https://openalex.org/W4392965271","https://openalex.org/W4393314452","https://openalex.org/W4396217748","https://openalex.org/W4401521626","https://openalex.org/W4404347348","https://openalex.org/W4408535507","https://openalex.org/W4408967875"],"related_works":["https://openalex.org/W2120417090","https://openalex.org/W2007339547","https://openalex.org/W4206713524","https://openalex.org/W2033108050","https://openalex.org/W1965554264","https://openalex.org/W2301851340","https://openalex.org/W372931616","https://openalex.org/W2127161083","https://openalex.org/W2188993073","https://openalex.org/W1509385305"],"abstract_inverted_index":{"Integrated":[0],"understanding":[1],"of":[2,12,70,154,165,190,198,202,229],"pharmacokinetics":[3],"(PK)":[4],"and":[5,42,72,75,108,133],"pharmacodynamics":[6],"(PD)":[7],"is":[8],"a":[9,37,52,83,96,104,148,199,223],"key":[10],"aspect":[11],"successful":[13],"drug":[14,20,39,84,233],"discovery.":[15],"Yet":[16],"in":[17,35,86,95,162,181],"generative":[18,38,231],"computational":[19,232],"design,":[21],"the":[22,45,78,112,116,123,142,152,166,178,182,188,191,196,206,226],"focus":[23],"often":[24],"lies":[25],"on":[26,205],"optimizing":[27,139],"potency.":[28],"Here":[29],"we":[30,43],"integrate":[31],"PK":[32,67,106,132,149,171,183],"property":[33],"predictions":[34,218],"DrugEx,":[36],"design":[40],"framework":[41,99],"explore":[44],"generated":[46],"compounds'":[47],"PD":[48],"through":[49],"simulations":[50],"with":[51,103,130,168,177,219],"quantitative":[53],"systems":[54],"pharmacology":[55],"(QSP)":[56],"model.":[57],"Quantitative":[58],"structure-property":[59],"relationship":[60],"models":[61,89],"were":[62,90],"developed":[63],"to":[64,92,100,141,175],"predict":[65],"molecule":[66],"(clearance,":[68],"volume":[69],"distribution":[71],"unbound":[73],"fraction)":[74],"affinity":[76,110,134,140,217],"for":[77,111,126,225],"Adenosine":[79],"A<sub>2A</sub>R":[80],"receptor":[81],"(A<sub>2A</sub>R),":[82],"target":[85],"immuno-oncology.":[87],"These":[88],"used":[91],"score":[93],"compounds":[94,167],"reinforcement":[97],"learning":[98],"generate":[101],"molecules":[102,129],"specific":[105],"profile":[107],"high":[109],"A<sub>2A</sub>R.":[113],"We":[114,136,186],"predicted":[115,170,207],"expected":[117],"tumor":[118,208],"growth":[119],"inhibition":[120],"profiles":[121],"using":[122],"QSP":[124,192],"model":[125,193],"selected":[127],"candidate":[128],"varying":[131],"profiles.":[135],"show":[137],"that":[138,157],"A<sub>2A</sub>R,":[143],"while":[144],"minimizing":[145],"or":[146],"maximizing":[147],"property,":[150],"shifts":[151],"type":[153],"molecular":[155],"scaffolds":[156],"are":[158],"generated.":[159],"The":[160],"difference":[161],"physicochemical":[163],"properties":[164,204],"different":[169],"parameters":[172],"was":[173],"found":[174],"correspond":[176],"differences":[179],"observed":[180],"data":[184],"set.":[185],"demonstrated":[187],"use":[189],"by":[194],"simulating":[195],"effect":[197],"broad":[200],"range":[201],"compound":[203],"volume.":[209],"In":[210],"conclusion,":[211],"our":[212],"proposed":[213],"integrated":[214],"workflow":[215],"incorporating":[216],"PKPD":[220],"may":[221],"provide":[222],"template":[224],"next":[227],"generation":[228],"advanced":[230],"design.":[234]},"counts_by_year":[{"year":2025,"cited_by_count":5}],"updated_date":"2026-03-11T14:59:36.786465","created_date":"2025-10-10T00:00:00"}