{"id":"https://openalex.org/W635645792","doi":null,"title":"Discovery and Characterization of Novel Inhibitors of the Prostaglandin E2 Pathway","display_name":"Discovery and Characterization of Novel Inhibitors of the Prostaglandin E2 Pathway","publication_year":2013,"publication_date":"2013-01-01","ids":{"openalex":"https://openalex.org/W635645792","mag":"635645792"},"language":"en","primary_location":{"id":"pmh:oai:repository.arizona.edu:10150/268614","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/10150/268614","pdf_url":null,"source":{"id":"https://openalex.org/S4306400271","display_name":"UA Campus Repository (The University of Arizona)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I138006243","host_organization_name":"University of Arizona","host_organization_lineage":["https://openalex.org/I138006243"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"Electronic Dissertation"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"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/A5102865018","display_name":"Hui-Hua Chang","orcid":"https://orcid.org/0000-0001-6369-0326","observed_orcids":["https://orcid.org/0000-0001-6369-0326"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Hui-Hua Chang","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-6369-0326","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5102865018"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"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/T10678","display_name":"Inflammatory mediators and NSAID effects","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10678","display_name":"Inflammatory mediators and NSAID effects","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.0012000000569969416,"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/T10211","display_name":"Computational Drug Discovery Methods","score":9.999999747378752e-05,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/mpges-1-inhibitors","display_name":"mPGES-1 inhibitors","score":0.7889999747276306},{"id":"https://openalex.org/keywords/prostaglandin-e2","display_name":"prostaglandin E2","score":0.921999990940094},{"id":"https://openalex.org/keywords/cyclooxygenase-2","display_name":"cyclooxygenase-2","score":0.8209999799728394},{"id":"https://openalex.org/keywords/anticancer-activity","display_name":"anticancer activity","score":0.5830000042915344},{"id":"https://openalex.org/keywords/mouse-xenograft-model","display_name":"xenograft mouse model","score":0.7570000290870667},{"id":"https://openalex.org/keywords/kinase-inhibition","display_name":"kinase inhibition","score":0.6859999895095825},{"id":"https://openalex.org/keywords/arachidonic-acid-metabolism","display_name":"arachidonic acid metabolism","score":0.9300000071525574},{"id":"https://openalex.org/keywords/pharmacophore-model","display_name":"pharmacophore model","score":0.5270000100135803},{"id":"https://openalex.org/keywords/cancer-therapeutics","display_name":"cancer therapeutics","score":0.6000000238418579},{"id":"https://openalex.org/keywords/mk-886","display_name":"MK-886","score":0.8009999990463257}],"concepts":[{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.39140981435775757},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3535873293876648}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:repository.arizona.edu:10150/268614","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/10150/268614","pdf_url":null,"source":{"id":"https://openalex.org/S4306400271","display_name":"UA Campus Repository (The University of Arizona)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I138006243","host_organization_name":"University of Arizona","host_organization_lineage":["https://openalex.org/I138006243"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"Electronic Dissertation"},{"id":"mag:635645792","doi":null,"is_oa":false,"landing_page_url":"http://arizona.openrepository.com/arizona/handle/10150/268614","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9763000011444092}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":221,"referenced_works":["https://openalex.org/W1487971131","https://openalex.org/W1489022916","https://openalex.org/W1497376376","https://openalex.org/W1514189093","https://openalex.org/W1527859504","https://openalex.org/W1532612328","https://openalex.org/W1540140680","https://openalex.org/W1552554367","https://openalex.org/W1552818500","https://openalex.org/W1555211583","https://openalex.org/W1562714701","https://openalex.org/W1577709580","https://openalex.org/W1597512265","https://openalex.org/W1602331691","https://openalex.org/W1616777268","https://openalex.org/W1648593433","https://openalex.org/W1672254856","https://openalex.org/W1802931340","https://openalex.org/W1868766650","https://openalex.org/W1964464231","https://openalex.org/W1967641836","https://openalex.org/W1967784191","https://openalex.org/W1969247204","https://openalex.org/W1970050679","https://openalex.org/W1976841921","https://openalex.org/W1979654645","https://openalex.org/W1979925150","https://openalex.org/W1980990431","https://openalex.org/W1981816788","https://openalex.org/W1983168018","https://openalex.org/W1983769980","https://openalex.org/W1986240377","https://openalex.org/W1987826058","https://openalex.org/W1988675408","https://openalex.org/W1988689895","https://openalex.org/W1989256917","https://openalex.org/W1990078462","https://openalex.org/W1990481894","https://openalex.org/W1990902085","https://openalex.org/W1993148712","https://openalex.org/W1994140458","https://openalex.org/W1994271130","https://openalex.org/W1994452548","https://openalex.org/W1995487106","https://openalex.org/W1996692411","https://openalex.org/W1996810761","https://openalex.org/W1997241564","https://openalex.org/W1997299718","https://openalex.org/W1998659041","https://openalex.org/W1999208756","https://openalex.org/W2000111352","https://openalex.org/W2000653578","https://openalex.org/W2000675841","https://openalex.org/W2003101243","https://openalex.org/W2004684605","https://openalex.org/W2006306072","https://openalex.org/W2007043238","https://openalex.org/W2007187686","https://openalex.org/W2009141757","https://openalex.org/W2010112169","https://openalex.org/W2010713047","https://openalex.org/W2011559907","https://openalex.org/W2013777179","https://openalex.org/W2014306540","https://openalex.org/W2014655159","https://openalex.org/W2015930054","https://openalex.org/W2016011980","https://openalex.org/W2016264364","https://openalex.org/W2018740272","https://openalex.org/W2020563114","https://openalex.org/W2024333268","https://openalex.org/W2028129603","https://openalex.org/W2030242710","https://openalex.org/W2031685248","https://openalex.org/W2032496322","https://openalex.org/W2032607036","https://openalex.org/W2033029295","https://openalex.org/W2033630180","https://openalex.org/W2034498760","https://openalex.org/W2036123458","https://openalex.org/W2036299072","https://openalex.org/W2036610614","https://openalex.org/W2037640656","https://openalex.org/W2038126877","https://openalex.org/W2039224704","https://openalex.org/W2040399413","https://openalex.org/W2040448204","https://openalex.org/W2044939825","https://openalex.org/W2045481712","https://openalex.org/W2045648679","https://openalex.org/W2048670117","https://openalex.org/W2048938127","https://openalex.org/W2053017995","https://openalex.org/W2055169387","https://openalex.org/W2056197566","https://openalex.org/W2056772956","https://openalex.org/W2057268626","https://openalex.org/W2057908592","https://openalex.org/W2058298545","https://openalex.org/W2060132531","https://openalex.org/W2060524491","https://openalex.org/W2061563398","https://openalex.org/W2062035346","https://openalex.org/W2062818585","https://openalex.org/W2064497840","https://openalex.org/W2064546820","https://openalex.org/W2064611947","https://openalex.org/W2064702379","https://openalex.org/W2064991073","https://openalex.org/W2066504511","https://openalex.org/W2066998725","https://openalex.org/W2067525135","https://openalex.org/W2069297347","https://openalex.org/W2070719504","https://openalex.org/W2071062350","https://openalex.org/W2072000048","https://openalex.org/W2073332085","https://openalex.org/W2073738021","https://openalex.org/W2074069372","https://openalex.org/W2076272189","https://openalex.org/W2077641423","https://openalex.org/W2077827642","https://openalex.org/W2078905435","https://openalex.org/W2079398727","https://openalex.org/W2079845012","https://openalex.org/W2081428891","https://openalex.org/W2081858756","https://openalex.org/W2082990300","https://openalex.org/W2083362070","https://openalex.org/W2085649523","https://openalex.org/W2090106927","https://openalex.org/W2094402002","https://openalex.org/W2095413208","https://openalex.org/W2095721808","https://openalex.org/W2096564111","https://openalex.org/W2096874183","https://openalex.org/W2097705351","https://openalex.org/W2098576049","https://openalex.org/W2099885559","https://openalex.org/W2100910673","https://openalex.org/W2101449587","https://openalex.org/W2102144390","https://openalex.org/W2104701964","https://openalex.org/W2105709072","https://openalex.org/W2106293055","https://openalex.org/W2109880539","https://openalex.org/W2111199059","https://openalex.org/W2111598062","https://openalex.org/W2113557359","https://openalex.org/W2114916777","https://openalex.org/W2115476193","https://openalex.org/W2116205530","https://openalex.org/W2117169037","https://openalex.org/W2117692326","https://openalex.org/W2118783753","https://openalex.org/W2119629574","https://openalex.org/W2120002897","https://openalex.org/W2120147264","https://openalex.org/W2120673934","https://openalex.org/W2121968614","https://openalex.org/W2123105952","https://openalex.org/W2124212354","https://openalex.org/W2125037484","https://openalex.org/W2125068995","https://openalex.org/W2125471013","https://openalex.org/W2125594974","https://openalex.org/W2129049437","https://openalex.org/W2129357350","https://openalex.org/W2129935236","https://openalex.org/W2130389194","https://openalex.org/W2130544027","https://openalex.org/W2132529497","https://openalex.org/W2134234269","https://openalex.org/W2135166720","https://openalex.org/W2136638726","https://openalex.org/W2138323828","https://openalex.org/W2138341116","https://openalex.org/W2138381757","https://openalex.org/W2139941310","https://openalex.org/W2141383117","https://openalex.org/W2144639685","https://openalex.org/W2145218740","https://openalex.org/W2146388445","https://openalex.org/W2146684665","https://openalex.org/W2147330842","https://openalex.org/W2147923982","https://openalex.org/W2148358344","https://openalex.org/W2148545400","https://openalex.org/W2148558073","https://openalex.org/W2148790437","https://openalex.org/W2148888228","https://openalex.org/W2151036184","https://openalex.org/W2152064969","https://openalex.org/W2153655497","https://openalex.org/W2155087173","https://openalex.org/W2155913937","https://openalex.org/W2156881931","https://openalex.org/W2157341902","https://openalex.org/W2158131645","https://openalex.org/W2158960911","https://openalex.org/W2158968701","https://openalex.org/W2161740453","https://openalex.org/W2163756514","https://openalex.org/W2165011857","https://openalex.org/W2166667647","https://openalex.org/W2167029659","https://openalex.org/W2167199734","https://openalex.org/W2167910100","https://openalex.org/W2168035069","https://openalex.org/W2168051211","https://openalex.org/W2168125951","https://openalex.org/W2169249687","https://openalex.org/W2170736848","https://openalex.org/W2182692795","https://openalex.org/W2188406439","https://openalex.org/W2320853648","https://openalex.org/W2330496155","https://openalex.org/W2336169581","https://openalex.org/W2409628508","https://openalex.org/W2953194867","https://openalex.org/W4406066000"],"related_works":["https://openalex.org/W2322643264","https://openalex.org/W2057268626","https://openalex.org/W2002887511","https://openalex.org/W4295678276","https://openalex.org/W1575542453","https://openalex.org/W4205263285","https://openalex.org/W2315397689","https://openalex.org/W2060524491","https://openalex.org/W2060132531","https://openalex.org/W2065812194"],"abstract_inverted_index":{"Microsomal":[0],"prostaglandin":[1,16],"E":[2],"synthase-1":[3],"(mPGES-1)":[4],"is":[5],"the":[6,13,114,134,145,163,171,182,196,258,269,312,336],"terminal":[7],"enzyme":[8],"following":[9],"cyclooxygenase-2":[10],"(COX-2)":[11],"for":[12,27,153,225,261],"production":[14],"of":[15,41,83,144,165,167,195,199,238,265,272,285,307,329,338],"E\u2082(PGE\u2082),":[17],"and":[18,61,103,169,214],"has":[19],"been":[20],"identified":[21,48,304,326],"as":[22,91,222],"a":[23,43,73,80,155,186,236,278,301,305],"novel":[24,37,327],"therapeutic":[25,270],"target":[26,279],"cancers.":[28],"From":[29],"an":[30],"in":[31,65,127,140,149,185,202,241,311],"silico":[32],"screen":[33],"aimed":[34],"at":[35],"developing":[36],"small":[38],"molecule":[39],"inhibitors":[40],"mPGES-1,":[42],"2-aminothiazole":[44],"compound":[45,94],"PGE0001":[46,102,168,226],"was":[47,175,190],"from":[49],"13":[50],"putative":[51],"hits":[52],"based":[53,71],"on":[54,72],"its":[55],"ability":[56],"to":[57,161,193,234,245,292,295,319,341],"reduce":[58],"cellular":[59],"PGE\u2082":[60,107,139,172,183,203,262],"minimal":[62],"COX-2":[63],"inhibition":[64,264],"vitro.":[66],"Utilizing":[67],"drug":[68],"design":[69],"strategies":[70],"4-point":[74],"pharmacophore":[75],"model,":[76],"we":[77,207,303,325],"also":[78,136,276],"discovered":[79],"new":[81],"series":[82],"compounds":[84,116,122,135,146,231,298,331],"exhibiting":[85],"superior":[86],"potency":[87],"without":[88],"inhibiting":[89],"COX-2,":[90],"exemplified":[92],"by":[93,289],"PGE0056.":[95,228],"In":[96,159,323],"multiple":[97],"cancer":[98],"cell":[99],"lines,":[100],"both":[101],"PGE0056":[104],"reduced":[105,138],"cytokine-stimulated":[106],"release":[108],"with":[109,133,332],"submicromolar":[110],"EC\u2085\u2080":[111],"values,":[112],"although":[113,335],"two":[115],"exhibited":[117],"differential":[118],"kinetics.":[119],"Importantly,":[120],"these":[121,230,250,286,297],"showed":[123],"promising":[124],"anti-tumor":[125,333],"effects":[126],"xenograft":[128],"mouse":[129],"models.":[130],"Mice":[131],"injected":[132],"had":[137],"serum.":[141],"Surprisingly,":[142],"none":[143],"inhibited":[147],"mPGES-1":[148,157],"cell-free":[150],"assays,":[151],"except":[152],"MK-886,":[154],"reported":[156],"inhibitor.":[158],"order":[160],"determine":[162],"mechanisms":[164,259,337],"action":[166,339],"PGE0056,":[170],"synthesis":[173],"cascade":[174],"extensively":[176],"examined.":[177],"Immunoblotting":[178],"analysis":[179,291],"suggested":[180],"that":[181],"reduction":[184],"short":[187],"time":[188],"frame":[189],"not":[191,255],"due":[192,244],"alteration":[194],"protein":[197],"level":[198],"enzymes":[200,309],"involved":[201,310],"synthesis/metabolism.":[204],"So":[205],"far,":[206],"have":[208],"excluded":[209],"upstream":[210],"COX-1/2,":[211],"phospholipase":[212],"A\u2082,":[213],"other":[215,308],"PGE":[216],"synthases":[217],"(mPGES-2":[218],"&":[219],"cytosolic":[220],"PGES)":[221],"major":[223],"targets":[224,253,294],"or":[227],"Interestingly,":[229],"were":[232],"found":[233],"inhibit":[235],"number":[237],"kinases":[239],"implicated":[240],"cancer,":[242],"presumably":[243],"their":[246],"structural":[247],"feature.":[248],"Although":[249],"alternative":[251],"kinase":[252],"may":[254,267],"sufficiently":[256],"explain":[257],"responsible":[260],"reduction,":[263],"them":[266],"strengthen":[268],"potential":[271],"our":[273],"compounds.":[274],"We":[275],"implemented":[277],"pull-down":[280],"approach":[281],"using":[282],"biotinylated":[283],"derivatives":[284],"compounds,":[287],"followed":[288],"proteomic":[290],"isolate":[293],"which":[296,317],"bind.":[299],"As":[300],"result,":[302],"couple":[306],"arachidonic":[313],"acid":[314],"metabolic":[315],"pathway,":[316],"need":[318],"be":[320,342],"further":[321],"validated.":[322],"summary,":[324],"classes":[328],"anti-inflammatory":[330],"activity,":[334],"remain":[340],"clarified.":[343]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}