{"id":"https://openalex.org/W1989772178","doi":"https://doi.org/10.1021/ar700155p","title":"Function-Oriented Synthesis, Step Economy, and Drug Design","display_name":"Function-Oriented Synthesis, Step Economy, and Drug Design","publication_year":2007,"publication_date":"2007-12-27","ids":{"openalex":"https://openalex.org/W1989772178","doi":"https://doi.org/10.1021/ar700155p","mag":"1989772178","pmid":"https://pubmed.ncbi.nlm.nih.gov/18159936"},"language":"en","primary_location":{"id":"doi:10.1021/ar700155p","doi":"https://doi.org/10.1021/ar700155p","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ar700155p","pdf_url":null,"source":{"id":"https://openalex.org/S145378405","display_name":"Accounts of Chemical Research","issn_l":"0001-4842","issn":["0001-4842","1520-4898"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-2","ki-jl-1","medline","norway-1","poland-200","russia-white-list-1"],"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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Accounts of Chemical Research","raw_type":"journal-article"},"volume":null,"type":"review","indexed_in":["crossref","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/A5060002438","display_name":"Paul A. Wender","orcid":"https://orcid.org/0000-0001-6319-2829","observed_orcids":["https://orcid.org/0000-0001-6319-2829"]},"institutions":[{"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":"Paul A. Wender","raw_affiliation_strings":["Department of Chemistry, Stanford University, Stanford, California 94305-5080","Department of Chemistry; Stanford University; Stanford California 94305-5080 USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Stanford University, Stanford, California 94305-5080","institution_ids":["https://openalex.org/I97018004"]},{"raw_affiliation_string":"Department of Chemistry; Stanford University; Stanford California 94305-5080 USA","institution_ids":["https://openalex.org/I97018004"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012762292","display_name":"Vishal A. Verma","orcid":"https://orcid.org/0000-0001-7600-4372","observed_orcids":["https://orcid.org/0000-0001-7600-4372"]},"institutions":[{"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":"Vishal A. Verma","raw_affiliation_strings":["Department of Chemistry, Stanford University, Stanford, California 94305-5080"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Stanford University, Stanford, California 94305-5080","institution_ids":["https://openalex.org/I97018004"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5084917931","display_name":"Thomas J. Paxton","orcid":null,"observed_orcids":[]},"institutions":[{"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":"Thomas J. Paxton","raw_affiliation_strings":["Department of Chemistry, Stanford University, Stanford, California 94305-5080"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Stanford University, Stanford, California 94305-5080","institution_ids":["https://openalex.org/I97018004"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5075200671","display_name":"Thomas H. Pillow","orcid":"https://orcid.org/0000-0001-7300-1002","observed_orcids":["https://orcid.org/0000-0001-7300-1002"]},"institutions":[{"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":"Thomas H. Pillow","raw_affiliation_strings":["Department of Chemistry, Stanford University, Stanford, California 94305-5080"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, Stanford University, Stanford, California 94305-5080","institution_ids":["https://openalex.org/I97018004"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I97018004"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":1.3912,"has_fulltext":false,"cited_by_count":1207,"citation_normalized_percentile":{"value":0.79044118,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":99,"max":100},"biblio":{"volume":"41","issue":"1","first_page":"40","last_page":"49"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.16940000653266907,"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"}},"topics":[{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.16940000653266907,"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":0.15770000219345093,"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/T13971","display_name":"Isoquinoline Alkaloid Synthesis","score":0.15559999644756317,"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/step-economy","display_name":"step economy","score":0.9020000100135803},{"id":"https://openalex.org/keywords/drug-design","display_name":"drug design","score":0.7419999837875366},{"id":"https://openalex.org/keywords/natural-product-leads","display_name":"natural product leads","score":0.8640000224113464},{"id":"https://openalex.org/keywords/multidrug-resistance","display_name":"multidrug resistance","score":0.8730000257492065},{"id":"https://openalex.org/keywords/anticancer-agents","display_name":"anticancer agents","score":0.8849999904632568},{"id":"https://openalex.org/keywords/microtubule-stabilization","display_name":"microtubule stabilization","score":0.7950000166893005},{"id":"https://openalex.org/keywords/cell-penetrating-peptides","display_name":"cell-penetrating peptides","score":0.8600000143051147},{"id":"https://openalex.org/keywords/drug-delivery-systems","display_name":"drug delivery systems","score":0.9549999833106995},{"id":"https://openalex.org/keywords/scaffold-design","display_name":"scaffold design","score":0.42899999022483826}],"concepts":[{"id":"https://openalex.org/C2779396153","wikidata":"https://www.wikidata.org/wiki/Q901227","display_name":"Natural product","level":2,"score":0.5533099174499512},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5009524822235107},{"id":"https://openalex.org/C14036430","wikidata":"https://www.wikidata.org/wiki/Q3736076","display_name":"Function (biology)","level":2,"score":0.4961410462856293},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4525338113307953},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.2236645519733429},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.18755564093589783},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.1651722490787506},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.10016003251075745},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.07601404190063477}],"mesh":[{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000191","qualifier_name":"economics","is_major_topic":true},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D001685","descriptor_name":"Biological Factors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D001685","descriptor_name":"Biological Factors","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":true},{"descriptor_ui":"D004337","descriptor_name":"Drug Carriers","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":false},{"descriptor_ui":"D004337","descriptor_name":"Drug Carriers","qualifier_ui":"Q000191","qualifier_name":"economics","is_major_topic":false},{"descriptor_ui":"D004337","descriptor_name":"Drug Carriers","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D008968","descriptor_name":"Molecular Conformation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D013237","descriptor_name":"Stereoisomerism","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/ar700155p","doi":"https://doi.org/10.1021/ar700155p","is_oa":false,"landing_page_url":"https://doi.org/10.1021/ar700155p","pdf_url":null,"source":{"id":"https://openalex.org/S145378405","display_name":"Accounts of Chemical Research","issn_l":"0001-4842","issn":["0001-4842","1520-4898"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-a","jufo-2","ki-jl-1","medline","norway-1","poland-200","russia-white-list-1"],"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":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Accounts of Chemical Research","raw_type":"journal-article"},{"id":"pmid:18159936","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/18159936","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":"Accounts of chemical research","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G433345679","display_name":null,"funder_award_id":"CA31845","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G844802523","display_name":null,"funder_award_id":"CA31841","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":61,"referenced_works":["https://openalex.org/W33831771","https://openalex.org/W1508881953","https://openalex.org/W1530826051","https://openalex.org/W1858568413","https://openalex.org/W1963566065","https://openalex.org/W1964870105","https://openalex.org/W1967925880","https://openalex.org/W1968248620","https://openalex.org/W1976137090","https://openalex.org/W1980008462","https://openalex.org/W1983338160","https://openalex.org/W1983706370","https://openalex.org/W1993966814","https://openalex.org/W2000434705","https://openalex.org/W2004094156","https://openalex.org/W2008845432","https://openalex.org/W2014791743","https://openalex.org/W2014968675","https://openalex.org/W2024577422","https://openalex.org/W2027484859","https://openalex.org/W2027633428","https://openalex.org/W2030205108","https://openalex.org/W2034591113","https://openalex.org/W2038275196","https://openalex.org/W2041650635","https://openalex.org/W2042143995","https://openalex.org/W2044457708","https://openalex.org/W2055278617","https://openalex.org/W2062161850","https://openalex.org/W2066223233","https://openalex.org/W2068639744","https://openalex.org/W2075366970","https://openalex.org/W2076488165","https://openalex.org/W2079335891","https://openalex.org/W2082035334","https://openalex.org/W2086588270","https://openalex.org/W2091212017","https://openalex.org/W2091322807","https://openalex.org/W2092916795","https://openalex.org/W2093080690","https://openalex.org/W2109033521","https://openalex.org/W2111101552","https://openalex.org/W2111129774","https://openalex.org/W2111994795","https://openalex.org/W2115544008","https://openalex.org/W2117595922","https://openalex.org/W2119651360","https://openalex.org/W2122631316","https://openalex.org/W2123650819","https://openalex.org/W2130860350","https://openalex.org/W2132147724","https://openalex.org/W2141474275","https://openalex.org/W2172074189","https://openalex.org/W2185537993","https://openalex.org/W2273634359","https://openalex.org/W2865901846","https://openalex.org/W2949159129","https://openalex.org/W2950072512","https://openalex.org/W2950215543","https://openalex.org/W2951321851","https://openalex.org/W4230581021"],"related_works":["https://openalex.org/W2318815559","https://openalex.org/W2326310231","https://openalex.org/W2950604646","https://openalex.org/W2156060934","https://openalex.org/W3094333894","https://openalex.org/W3100389572","https://openalex.org/W2098932616","https://openalex.org/W2952073274","https://openalex.org/W2023058692","https://openalex.org/W2020091539"],"abstract_inverted_index":{"This":[0,109,134,352],"Account":[1],"provides":[2],"an":[3],"overview":[4],"and":[5,11,54,105,168,178,185,201,220,249,262,266,279,298,319,327],"examples":[6],"of":[7,78,84,103,143,189,215,264,281,291,332,339,357],"function-oriented":[8],"synthesis":[9,61,104,263,280],"(FOS)":[10],"its":[12],"increasingly":[13],"important":[14,145],"role":[15],"in":[16,24,162,180,195,206,212,221,309,324],"producing":[17],"therapeutic":[18,73],"leads":[19,32,345],"that":[20,62,81,159,191,230,253,305,320],"can":[21,90,111,192,306,321],"be":[22,91,193,322],"made":[23,194],"a":[25,59,85,141,153,196,213,310,325],"step-economical":[26,328],"fashion.":[27,329],"Biologically":[28],"active":[29,87,342],"natural":[30,46,146,155,343],"product":[31,147,156,344],"often":[33],"suffer":[34],"from":[35,45,247],"several":[36],"deficiencies.":[37],"Many":[38],"are":[39,50,67,202],"scarce":[40],"or":[41,94,287,293],"difficult":[42],"to":[43,58,115,140,204],"obtain":[44],"sources.":[47],"Often,":[48],"they":[49],"highly":[51],"complex":[52],"molecules":[53],"thus":[55],"not":[56,68],"amenable":[57],"practical":[60,113,197,326],"would":[63],"impact":[64],"supply.":[65],"Most":[66],"optimally":[69],"suitable":[70],"for":[71,101,128,285,336],"human":[72,216],"use.":[74],"The":[75,330],"central":[76],"principle":[77],"FOS":[79,135,258,271,333],"is":[80,152,225,239],"the":[82,124,170,260,277,289,337,355],"function":[83],"biologically":[86,341],"lead":[88,158,229],"structure":[89],"recapitulated,":[92],"tuned,":[93],"greatly":[95],"enhanced":[96],"with":[97,119,314,349],"simpler":[98],"scaffolds":[99],"designed":[100,184],"ease":[102],"also":[106,175],"synthetic":[107,129],"innovation.":[108],"approach":[110,136,353],"provide":[112],"access":[114],"new":[116],"(designed)":[117],"structures":[118],"novel":[120,364],"activities":[121],"while":[122,361],"at":[123,276],"same":[125],"time":[126],"allowing":[127],"innovation":[130],"by":[131],"target":[132],"design.":[133],"has":[137,273,334],"been":[138,255,274],"applied":[139],"number":[142],"therapeutically":[144,363],"leads.":[148],"For":[149],"example,":[150],"bryostatin":[151,190,205],"unique":[154],"anticancer":[157,228],"restores":[160],"apoptosis":[161],"cancer":[163,217],"cells,":[164],"reverses":[165],"multidrug":[166],"resistance,":[167],"bolsters":[169],"immune":[171],"system.":[172],"Remarkably,":[173],"it":[174,238],"improves":[176],"cognition":[177],"memory":[179],"animals.":[181],"We":[182,300],"have":[183,254,301],"synthesized":[186,323],"simplified":[187,347],"analogs":[188,348],"fashion":[198,312],"(pilot":[199],"scale)":[200],"superior":[203,311,350],"numerous":[207],"assays":[208],"including":[209],"growth":[210],"inhibition":[211],"variety":[214],"cell":[218,243],"lines":[219],"animal":[222],"models.":[223],"Laulimalide":[224,245],"another":[226],"exciting":[227],"stabilizes":[231],"microtubules,":[232],"like":[233],"paclitaxel,":[234,237],"but":[235],"unlike":[236],"effective":[240],"against":[241],"multidrug-resistant":[242],"lines.":[244],"suffers":[246],"availability":[248],"stability":[250],"problems,":[251],"issues":[252],"addressed":[256],"using":[257],"through":[259],"design":[261,278],"stable":[265],"efficacious":[267],"laulimalide":[268],"analogs.":[269],"Another":[270],"program":[272],"directed":[275],"drug":[282,294],"delivery":[283],"systems":[284],"enabling":[286],"enhancing":[288],"uptake":[290],"drugs":[292],"candidates":[295],"into":[296,346],"cells":[297],"tissue.":[299],"generated":[302],"improved":[303],"transporters":[304],"deliver":[307],"agents":[308],"compared":[313],"naturally":[315],"occurring":[316],"cell-penetrating":[317],"peptides":[318],"use":[331],"allowed":[335],"translation":[338],"exciting,":[340],"function.":[351],"enables":[354],"development":[356],"synthetically":[358],"innovative":[359],"strategies":[360],"targeting":[362],"structures.":[365]},"counts_by_year":[{"year":2026,"cited_by_count":49},{"year":2025,"cited_by_count":58},{"year":2024,"cited_by_count":58},{"year":2023,"cited_by_count":43},{"year":2022,"cited_by_count":54},{"year":2021,"cited_by_count":60},{"year":2020,"cited_by_count":60},{"year":2019,"cited_by_count":76},{"year":2018,"cited_by_count":85},{"year":2017,"cited_by_count":76},{"year":2016,"cited_by_count":87},{"year":2015,"cited_by_count":76},{"year":2014,"cited_by_count":86},{"year":2013,"cited_by_count":80},{"year":2012,"cited_by_count":87}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}