{"id":"https://openalex.org/W1480437404","doi":"https://doi.org/10.1016/s0021-9258(19)42149-2","title":"N-(Phosphonacetyl)-l-Aspartate, a Potent Transition State Analog Inhibitor of Aspartate Transcarbamylase, Blocks Proliferation of Mammalian Cells in Culture","display_name":"N-(Phosphonacetyl)-l-Aspartate, a Potent Transition State Analog Inhibitor of Aspartate Transcarbamylase, Blocks Proliferation of Mammalian Cells in Culture","publication_year":1974,"publication_date":"1974-11-01","ids":{"openalex":"https://openalex.org/W1480437404","doi":"https://doi.org/10.1016/s0021-9258(19)42149-2","mag":"1480437404","pmid":"https://pubmed.ncbi.nlm.nih.gov/4371054"},"language":"en","primary_location":{"id":"doi:10.1016/s0021-9258(19)42149-2","doi":"https://doi.org/10.1016/s0021-9258(19)42149-2","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0021-9258(19)42149-2","pdf_url":null,"source":{"id":"https://openalex.org/S140251998","display_name":"Journal of Biological Chemistry","issn_l":"0021-9258","issn":["0021-9258","1067-8816","1083-351X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"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 Biological Chemistry","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1016/s0021-9258(19)42149-2","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5072814093","display_name":"Elizabeth A. Swyryd","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210137306","display_name":"Stanford Medicine","ror":"https://ror.org/03mtd9a03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]},{"id":"https://openalex.org/I97018004","display_name":"Stanford University","ror":"https://ror.org/00f54p054","country_code":"US","type":"education","lineage":["https://openalex.org/I97018004"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Elizabeth A. Swyryd","raw_affiliation_strings":["From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305","institution_ids":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014266640","display_name":"Sally S. Seaver","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210137306","display_name":"Stanford Medicine","ror":"https://ror.org/03mtd9a03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]},{"id":"https://openalex.org/I97018004","display_name":"Stanford University","ror":"https://ror.org/00f54p054","country_code":"US","type":"education","lineage":["https://openalex.org/I97018004"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sally S. Seaver","raw_affiliation_strings":["From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305","institution_ids":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5080998429","display_name":"George Robert Stark","orcid":"https://orcid.org/0000-0002-8776-9597","observed_orcids":["https://orcid.org/0000-0002-8776-9597"]},"institutions":[{"id":"https://openalex.org/I4210137306","display_name":"Stanford Medicine","ror":"https://ror.org/03mtd9a03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]},{"id":"https://openalex.org/I97018004","display_name":"Stanford University","ror":"https://ror.org/00f54p054","country_code":"US","type":"education","lineage":["https://openalex.org/I97018004"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"George R. Stark","raw_affiliation_strings":["From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305","institution_ids":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":3430,"currency":"USD","value_usd":3430},"apc_paid":{"value":3430,"currency":"USD","value_usd":3430},"fwci":3.232,"has_fulltext":false,"cited_by_count":205,"citation_normalized_percentile":{"value":0.92094448,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":98},"biblio":{"volume":"249","issue":"21","first_page":"6945","last_page":"6950"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":1.0,"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/T12827","display_name":"Biochemical and Molecular Research","score":1.0,"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/T14099","display_name":"Synthesis and Characterization of Heterocyclic Compounds","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"}},{"id":"https://openalex.org/T12770","display_name":"Amino Acid Enzymes and Metabolism","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1303","display_name":"Biochemistry"},"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/n-phosphonacetyl-l-aspartate","display_name":"N-(phosphonacetyl)-L-aspartate","score":0.9929999709129333},{"id":"https://openalex.org/keywords/aspartate-transcarbamoylase","display_name":"aspartate transcarbamylase","score":0.9509999752044678},{"id":"https://openalex.org/keywords/transition-state-analogue-inhibitors","display_name":"transition-state inhibitors","score":0.7820000052452087},{"id":"https://openalex.org/keywords/pyrimidine-biosynthesis","display_name":"pyrimidine synthesis","score":0.8320000171661377},{"id":"https://openalex.org/keywords/uridine-biosynthesis","display_name":"uridine biosynthesis","score":0.6259999871253967},{"id":"https://openalex.org/keywords/cell-proliferation-inhibition","display_name":"cell proliferation inhibition","score":0.9179999828338623},{"id":"https://openalex.org/keywords/cytotoxicity","display_name":"cytotoxicity","score":0.8140000104904175},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.7509999871253967},{"id":"https://openalex.org/keywords/enzyme-inhibition","display_name":"enzyme inhibition","score":0.5649999976158142},{"id":"https://openalex.org/keywords/carbamoyl-phosphate","display_name":"carbamoyl phosphate","score":0.6470000147819519}],"concepts":[{"id":"https://openalex.org/C197248121","wikidata":"https://www.wikidata.org/wiki/Q24724427","display_name":"Aspartate carbamoyltransferase","level":4,"score":0.6416372656822205},{"id":"https://openalex.org/C194232998","wikidata":"https://www.wikidata.org/wiki/Q1606712","display_name":"Transition (genetics)","level":3,"score":0.5404852628707886},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4296238124370575},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.35466769337654114},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.33283984661102295},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3266485035419464},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.27734071016311646},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.0918799340724945},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.06026649475097656},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.05473276972770691}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000882","descriptor_name":"Haplorhini","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001221","descriptor_name":"Aspartate Carbamoyltransferase","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D001224","descriptor_name":"Aspartic Acid","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D001224","descriptor_name":"Aspartic Acid","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D001639","descriptor_name":"Bicarbonates","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002219","descriptor_name":"Carbamates","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002250","descriptor_name":"Carbon Radioisotopes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002455","descriptor_name":"Cell Division","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002471","descriptor_name":"Cell Transformation, Neoplastic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002478","descriptor_name":"Cells, Cultured","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002852","descriptor_name":"Chromatography, Ion Exchange","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005347","descriptor_name":"Fibroblasts","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007668","descriptor_name":"Kidney","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008815","descriptor_name":"Mice, Inbred Strains","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009943","descriptor_name":"Organophosphorus Compounds","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010746","descriptor_name":"Phosphonoacetic Acid","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D013045","descriptor_name":"Species Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013539","descriptor_name":"Simian virus 40","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014316","descriptor_name":"Tritium","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014529","descriptor_name":"Uridine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D063065","descriptor_name":"Organophosphonates","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1016/s0021-9258(19)42149-2","doi":"https://doi.org/10.1016/s0021-9258(19)42149-2","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0021-9258(19)42149-2","pdf_url":null,"source":{"id":"https://openalex.org/S140251998","display_name":"Journal of Biological Chemistry","issn_l":"0021-9258","issn":["0021-9258","1067-8816","1083-351X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"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 Biological Chemistry","raw_type":"journal-article"},{"id":"pmid:4371054","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/4371054","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,"listed_in":[],"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":"The Journal of biological chemistry","raw_type":"Comparative Study"}],"best_oa_location":{"id":"doi:10.1016/s0021-9258(19)42149-2","doi":"https://doi.org/10.1016/s0021-9258(19)42149-2","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0021-9258(19)42149-2","pdf_url":null,"source":{"id":"https://openalex.org/S140251998","display_name":"Journal of Biological Chemistry","issn_l":"0021-9258","issn":["0021-9258","1067-8816","1083-351X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"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 Biological Chemistry","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.7246000170707703}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":18,"referenced_works":["https://openalex.org/W1506579504","https://openalex.org/W1561167748","https://openalex.org/W1589814349","https://openalex.org/W1635858559","https://openalex.org/W1658317722","https://openalex.org/W1866144427","https://openalex.org/W1976287604","https://openalex.org/W1981206454","https://openalex.org/W1995841839","https://openalex.org/W2014281089","https://openalex.org/W2015999520","https://openalex.org/W2053377706","https://openalex.org/W2075716816","https://openalex.org/W2081609898","https://openalex.org/W2157297912","https://openalex.org/W2331164589","https://openalex.org/W2416741417","https://openalex.org/W3006884173"],"related_works":["https://openalex.org/W1658317722","https://openalex.org/W1642886417","https://openalex.org/W1974449396","https://openalex.org/W2138948753","https://openalex.org/W1893840631","https://openalex.org/W170804473","https://openalex.org/W2077968115","https://openalex.org/W2101405369","https://openalex.org/W2100153775","https://openalex.org/W2088920535"],"abstract_inverted_index":{"Abstract":[0],"N-(phosphonacetyl)-l-aspartate":[1],"(PALA)":[2],"is":[3,39,69,100,107,138,151,175,219,284],"an":[4,196],"analog":[5],"of":[6,29,47,56,64,96,135,159,187,198,207,225,254,280],"the":[7,11,30,62,67,88,110,127,132,140,149,155,160,171,205,255,278,281],"activated":[8],"complex":[9],"for":[10,173,274],"reaction":[12],"catalyzed":[13],"by":[14,203,286],"aspartate":[15,291],"transcarbamylase":[16,292],"and":[17,26,35,91,183,213,267],"has":[18],"previously":[19],"been":[20],"shown":[21,41],"to":[22,42,143,154,195,221,261],"be":[23,43,124],"a":[24,44,287],"potent":[25,45],"specific":[27],"inhibitor":[28,46],"enzymes":[31],"from":[32,87,163,209,227],"Escherichia":[33],"coli":[34],"mouse":[36],"spleen.":[37],"PALA":[38,65,99,114,137,161,174,192,218,242,264],"now":[40],"de":[48],"novo":[49],"pyrimidine":[50],"nucleotide":[51],"biosynthesis":[52,118],"in":[53,59,66,109,139,148,193,235,247,265,277,290],"five":[54],"lines":[55],"mammalian":[57],"cells":[58,76,164,201,258],"culture.":[60],"When":[61,131],"concentration":[63,134,147],"medium":[68],"10-4":[70,97,104,142,262],"m,":[71,145],"simian":[72],"virus":[73],"40-transformed":[74],"hamster":[75,200,257],"do":[77],"not":[78],"divide":[79],"and,":[80],"within":[81],"about":[82,176],"2":[83],"days,":[84],"have":[85],"detached":[86],"culture":[89,266],"dishes":[90],"appear":[92],"dead.":[93],"The":[94,120],"toxicity":[95],"m":[98,105,180,191,217,263],"prevented":[101],"completely":[102],"if":[103],"uridine":[106],"present":[108],"medium,":[111],"showing":[112],"that":[113,241],"inhibits":[115,202],"uridylic":[116],"acid":[117],"specifically.":[119],"same":[121],"effect":[122],"can":[123],"observed":[125],"with":[126],"other":[128],"cell":[129,169],"lines.":[130],"external":[133,156],"radioactive":[136],"range":[141],"10-5":[144],"its":[146],"cytosol":[150],"approximately":[152,215],"equal":[153],"concentration.":[157],"Most":[158],"recovered":[162],"remains":[165],"undegraded.":[166],"In":[167],"crude":[168],"extracts,":[170],"Ki":[172],"1":[177,188],"x":[178,189],"10-9":[179],"at":[181],"37\u00b0":[182],"pH":[184],"7.5.":[185],"Addition":[186],"10-7":[190],"vitro":[194],"extract":[197],"transformed":[199],"60%":[204],"incorporation":[206,226],"radioactivity":[208],"CO2":[210],"into":[211],"UMP":[212],"CMP;":[214],"10-6":[216],"required":[220],"give":[222,231],"comparable":[223],"inhibition":[224,234],"carbamyl-P.":[228],"Higher":[229],"concentrations":[230],"virtually":[232],"complete":[233],"both":[236],"cases.":[237],"These":[238],"results":[239],"suggest":[240],"may":[243],"find":[244],"clinical":[245],"use":[246],"suppressing":[248],"cellular":[249],"proliferation.":[250],"A":[251],"small":[252],"number":[253],"virus-transformed":[256],"become":[259],"resistant":[260],"retain":[268],"resistance":[269],"after":[270],"they":[271],"are":[272],"grown":[273],"many":[275],"generations":[276],"absence":[279],"drug.":[282],"Resistance":[283],"accompanied":[285],"large":[288],"increase":[289],"activity.":[293]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":3},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":5},{"year":2019,"cited_by_count":4},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":3},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":2},{"year":2012,"cited_by_count":2}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}
