{"id":"https://openalex.org/W24018398","doi":null,"title":"Enzyme inhibition, polyglutamation, and the effect of LY231514 (MTA) on purine biosynthesis.","display_name":"Enzyme inhibition, polyglutamation, and the effect of LY231514 (MTA) on purine biosynthesis.","publication_year":1999,"publication_date":"1999-04-01","ids":{"openalex":"https://openalex.org/W24018398","mag":"24018398","pmid":"https://pubmed.ncbi.nlm.nih.gov/10598554"},"language":"en","primary_location":{"id":"pmid:10598554","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/10598554","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":"Seminars in oncology","raw_type":"Journal Article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111527711","display_name":"L G Mendelsohn","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I168537998","display_name":"Eli Lilly (United States)","ror":"https://ror.org/01qat3289","country_code":"US","type":"company","lineage":["https://openalex.org/I168537998"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"L G Mendelsohn","raw_affiliation_strings":["Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis 46285, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis 46285, USA","institution_ids":["https://openalex.org/I168537998"]}]},{"author_position":"middle","author":{"id":null,"display_name":"C Shih","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"C Shih","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047317434","display_name":"V. J. Chen","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"V J Chen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075722881","display_name":"Lillian L. Habeck","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"L L Habeck","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085880056","display_name":"Susan B. Gates","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"S B Gates","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5069411307","display_name":"Katherine A. Shackelford","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"K A Shackelford","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":1.1492,"has_fulltext":false,"cited_by_count":103,"citation_normalized_percentile":{"value":0.74439301,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":98},"biblio":{"volume":"26","issue":"2 Suppl 6","first_page":"42","last_page":"7"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":0.7534000277519226,"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":0.7534000277519226,"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/T10499","display_name":"Folate and B Vitamins Research","score":0.13449999690055847,"subfield":{"id":"https://openalex.org/subfields/2916","display_name":"Nutrition and Dietetics"},"field":{"id":"https://openalex.org/fields/29","display_name":"Nursing"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.019200000911951065,"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/pemetrexed","display_name":"pemetrexed","score":0.9769999980926514},{"id":"https://openalex.org/keywords/methotrexate-analogs","display_name":"methotrexate analogs","score":0.6769999861717224},{"id":"https://openalex.org/keywords/folylpolyglutamate-synthase","display_name":"FPGS","score":0.9909999966621399},{"id":"https://openalex.org/keywords/thymidylate-synthase","display_name":"thymidylate synthase","score":0.8299999833106995},{"id":"https://openalex.org/keywords/dihydrofolate-reductase","display_name":"dihydrofolate reductase","score":0.9980000257492065},{"id":"https://openalex.org/keywords/glycinamide-ribonucleotide-formyltransferase","display_name":"glycinamide ribonucleotide formyltransferase","score":0.9879999756813049},{"id":"https://openalex.org/keywords/purine-biosynthesis","display_name":"purine biosynthesis","score":0.8790000081062317},{"id":"https://openalex.org/keywords/lometrexol","display_name":"lometrexol","score":0.7419999837875366},{"id":"https://openalex.org/keywords/enzyme-inhibition","display_name":"enzyme inhibition","score":0.49900001287460327},{"id":"https://openalex.org/keywords/tight-binding-inhibitors","display_name":"tight-binding inhibitors","score":0.5540000200271606}],"concepts":[{"id":"https://openalex.org/C123321153","wikidata":"https://www.wikidata.org/wiki/Q22676802","display_name":"Thymidylate synthase","level":4,"score":0.8885218501091003},{"id":"https://openalex.org/C2781382166","wikidata":"https://www.wikidata.org/wiki/Q50573407","display_name":"Antifolate","level":4,"score":0.8320903778076172},{"id":"https://openalex.org/C2781320022","wikidata":"https://www.wikidata.org/wiki/Q417149","display_name":"Dihydrofolate reductase","level":3,"score":0.645173192024231},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.6042320132255554},{"id":"https://openalex.org/C2781059491","wikidata":"https://www.wikidata.org/wiki/Q422232","display_name":"Methotrexate","level":2,"score":0.5846667289733887},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.5494167804718018},{"id":"https://openalex.org/C169586020","wikidata":"https://www.wikidata.org/wiki/Q3780159","display_name":"Purine metabolism","level":3,"score":0.5025792121887207},{"id":"https://openalex.org/C2778397455","wikidata":"https://www.wikidata.org/wiki/Q50429865","display_name":"Antimetabolite","level":3,"score":0.4940376877784729},{"id":"https://openalex.org/C28212737","wikidata":"https://www.wikidata.org/wiki/Q5381543","display_name":"Enzyme assay","level":3,"score":0.43433311581611633},{"id":"https://openalex.org/C2776980637","wikidata":"https://www.wikidata.org/wiki/Q427492","display_name":"Enzyme inhibitor","level":3,"score":0.43197375535964966},{"id":"https://openalex.org/C2777289219","wikidata":"https://www.wikidata.org/wiki/Q7632154","display_name":"Substrate (aquarium)","level":2,"score":0.41099750995635986},{"id":"https://openalex.org/C2776476023","wikidata":"https://www.wikidata.org/wiki/Q188261","display_name":"Purine","level":3,"score":0.41011568903923035},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3482610583305359},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.33768391609191895},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.2510940432548523},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.17697978019714355},{"id":"https://openalex.org/C2780456651","wikidata":"https://www.wikidata.org/wiki/Q238512","display_name":"Fluorouracil","level":3,"score":0.08339366316795349},{"id":"https://openalex.org/C18903297","wikidata":"https://www.wikidata.org/wiki/Q7150","display_name":"Ecology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000068437","descriptor_name":"Pemetrexed","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000964","descriptor_name":"Antimetabolites, Antineoplastic","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D005493","descriptor_name":"Folic Acid Antagonists","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D005971","descriptor_name":"Glutamates","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D005971","descriptor_name":"Glutamates","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D006147","descriptor_name":"Guanine","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D006147","descriptor_name":"Guanine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006147","descriptor_name":"Guanine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D010453","descriptor_name":"Peptide Synthases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011099","descriptor_name":"Polyglutamic Acid","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011687","descriptor_name":"Purines","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D011687","descriptor_name":"Purines","qualifier_ui":"Q000096","qualifier_name":"biosynthesis","is_major_topic":false},{"descriptor_ui":"D013763","descriptor_name":"Tetrahydrofolates","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013763","descriptor_name":"Tetrahydrofolates","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false}],"locations_count":2,"locations":[{"id":"pmid:10598554","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/10598554","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":"Seminars in oncology","raw_type":"Journal Article"},{"id":"mag:24018398","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/10598554","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":null,"is_accepted":false,"is_published":false,"raw_source_name":"PubMed","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.8371999859809875,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":2,"referenced_works":["https://openalex.org/W2624159414","https://openalex.org/W4243325036"],"related_works":["https://openalex.org/W2073979951","https://openalex.org/W1573184761","https://openalex.org/W2084951620","https://openalex.org/W134960223","https://openalex.org/W51813618","https://openalex.org/W1594621311","https://openalex.org/W35048030","https://openalex.org/W1487023742","https://openalex.org/W2161777130","https://openalex.org/W1988007280"],"abstract_inverted_index":{"The":[0,38,72,112,186,222,282],"pyrrolopyrimidine-based":[1],"antifolate,":[2],"N-\u00bf4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl":[3],"]benzoyl\u00bfglutamic":[4],"acid,":[5],"LY231514":[6],"(MTA)":[7],"has":[8],"demonstrated":[9,262],"antitumor":[10,312],"activity":[11,43,55,223,313],"in":[12,121],"a":[13,143,153,305],"broad":[14,311],"array":[15],"of":[16,41,49,56,101,114,116,160,181,224,247,264,277,285,287,296,314],"human":[17,319],"tumors,":[18],"including":[19,251],"breast":[20],"cancer,":[21,23,27,31,33],"colon":[22],"non-small":[24],"cell":[25],"lung":[26],"head":[28],"and":[29,34,53,67,92,103,125,134,152,157,210,226,240,256,293],"neck":[30],"pancreatic":[32],"other":[35],"solid":[36],"tumors.":[37],"biochemical":[39],"basis":[40,307],"this":[42,220,315],"was":[44,200,204,212,235],"explored":[45],"by":[46,51,219,270],"measuring":[47],"activation":[48,286],"MTA":[50,57,78,131,136,192,203,225,239,288],"polyglutamation":[52],"the":[54,138,161,168,265,294,310],"to":[58,215,230,289,299],"inhibit":[59,231,300],"several":[60,117,232,248],"folate-dependent":[61,233,249,302],"enzymes:":[62],"thymidylate":[63,252],"synthase,":[64,253],"dihydrofolate":[65,254],"reductase,":[66,255],"glycinamide":[68],"ribonucleotide":[69],"formyltransferase":[70],"(GARFT).":[71],"enzyme":[73],"folylpolyglutamate":[74],"synthase":[75],"(FPGS)":[76],"activated":[77],"very":[79],"efficiently.":[80],"Using":[81],"FPGS":[82,209],"from":[83],"two":[84],"different":[85],"species,":[86],"Km":[87],"values":[88],"below":[89],"2":[90],"micromol/L":[91],"high":[93,124],"relative":[94],"first":[95],"order":[96],"rate":[97],"constants,":[98],"k'":[99],"(Vmax/Km)":[100],"6.4":[102],"13.7":[104],"compared":[105,120],"with":[106,273],"another":[107],"substrate,":[108],"lometrexol,":[109,195],"were":[110,119,137,165,184,190,243],"obtained.":[111],"formation":[113],"polyglutamates":[115,242,298],"antifolates":[118],"vitro":[122],"at":[123],"low":[126,130],"substrate":[127,173,207],"concentrations.":[128],"At":[129,171],"concentrations,":[132],"tetraglutamated":[133],"pentaglutamated":[135],"predominant":[139],"forms":[140,159],"identified":[141],"after":[142],"24-hour":[144],"incubation":[145],"period.":[146],"In":[147,237],"contrast,":[148],"only":[149,197],"diglutamyl":[150,198],"methotrexate":[151,199],"mixture":[154],"triglutamylated,":[155],"tetraglutamylated,":[156],"pentaglutamylated":[158],"GARFT":[162],"inhibitor":[163],"lometrexol":[164],"formed":[166],"under":[167],"same":[169],"conditions.":[170],"higher":[172],"concentrations":[174],"(20":[175],"micromol/L,":[176],"24":[177],"hours),":[178],"greater":[179],"amounts":[180],"each":[182],"product":[183],"formed.":[185],"major":[187],"metabolites,":[188],"however,":[189],"triglutamated":[191,194],"or":[193],"while":[196],"recovered.":[201],"Thus,":[202],"an":[205],"excellent":[206],"for":[208,308],"it":[211],"efficiently":[213],"metabolized":[214],"highly":[216,290],"polyglutamated":[217,228,291],"species":[218],"enzyme.":[221],"its":[227,241,274],"metabolites":[229,292],"enzymes":[234,303],"measured.":[236],"vitro,":[238],"potent,":[244],"tight-binding":[245],"inhibitors":[246],"enzymes,":[250],"GARFT.":[257],"Preliminary":[258],"cell-based":[259],"assays":[260],"(CCRF-CEM)":[261],"inhibition":[263],"purine":[266],"de":[267],"novo":[268],"pathway":[269],"MTA,":[271],"consistent":[272],"multitargeted":[275],"mechanism":[276],"action":[278],"against":[279,317],"tumor":[280,320],"cells.":[281],"combined":[283],"effects":[284],"potency":[295],"these":[297],"multiple":[301],"provide":[304],"mechanistic":[306],"understanding":[309],"compound":[316],"many":[318],"types.":[321]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":3},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":4},{"year":2014,"cited_by_count":6},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":5}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}
