{"id":"https://openalex.org/W136106025","doi":null,"title":"Design, Synthesis and Biological Evaluation of Non-Peptidic Small Molecular SMAC Mimetics as Potent IAP Inhibitors.","display_name":"Design, Synthesis and Biological Evaluation of Non-Peptidic Small Molecular SMAC Mimetics as Potent IAP Inhibitors.","publication_year":2008,"publication_date":"2008-01-01","ids":{"openalex":"https://openalex.org/W136106025","mag":"136106025"},"language":"en","primary_location":{"id":"pmh:oai:deepblue.lib.umich.edu:2027.42/61591","doi":null,"is_oa":true,"landing_page_url":"https://hdl.handle.net/2027.42/61591","pdf_url":"https://hdl.handle.net/2027.42/61591","source":{"id":"https://openalex.org/S4306400393","display_name":"Deep Blue (University of Michigan)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I27837315","host_organization_name":"University of Michigan","host_organization_lineage":["https://openalex.org/I27837315"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://hdl.handle.net/2027.42/61591","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5110080295","display_name":"Yuefeng Peng","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Yuefeng Peng","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5110080295"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"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/T10294","display_name":"Cell death mechanisms and regulation","score":0.9937000274658203,"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/T10294","display_name":"Cell death mechanisms and regulation","score":0.9937000274658203,"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/T10911","display_name":"Chemical Synthesis and Analysis","score":0.003599999938160181,"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/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.000699999975040555,"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/smac-mimetics","display_name":"IAP antagonists","score":0.9860000014305115},{"id":"https://openalex.org/keywords/xiap-inhibitors","display_name":"XIAP inhibitors","score":0.7419999837875366},{"id":"https://openalex.org/keywords/iap-inhibitors","display_name":"IAP inhibitors","score":0.7829999923706055},{"id":"https://openalex.org/keywords/apoptosis-resistance","display_name":"apoptosis resistance","score":0.5360000133514404},{"id":"https://openalex.org/keywords/caspase-8","display_name":"caspase-8","score":0.9010000228881836},{"id":"https://openalex.org/keywords/caspase-3","display_name":"caspase-3","score":0.9129999876022339},{"id":"https://openalex.org/keywords/caspase-9","display_name":"caspase-9","score":0.7229999899864197},{"id":"https://openalex.org/keywords/bir-domain","display_name":"BIR domain","score":0.6460000276565552},{"id":"https://openalex.org/keywords/tumor-cell-growth-inhibition","display_name":"tumor cell growth inhibition","score":0.675000011920929},{"id":"https://openalex.org/keywords/anticancer-drug-design","display_name":"anticancer drug design","score":0.5299999713897705}],"concepts":[{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.43570876121520996},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4273015260696411},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.3690241575241089},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3245247006416321},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.26930832862854004}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:deepblue.lib.umich.edu:2027.42/61591","doi":null,"is_oa":true,"landing_page_url":"https://hdl.handle.net/2027.42/61591","pdf_url":"https://hdl.handle.net/2027.42/61591","source":{"id":"https://openalex.org/S4306400393","display_name":"Deep Blue (University of Michigan)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I27837315","host_organization_name":"University of Michigan","host_organization_lineage":["https://openalex.org/I27837315"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},{"id":"mag:136106025","doi":null,"is_oa":false,"landing_page_url":"https://deepblue.lib.umich.edu/handle/2027.42/61591","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":{"id":"pmh:oai:deepblue.lib.umich.edu:2027.42/61591","doi":null,"is_oa":true,"landing_page_url":"https://hdl.handle.net/2027.42/61591","pdf_url":"https://hdl.handle.net/2027.42/61591","source":{"id":"https://openalex.org/S4306400393","display_name":"Deep Blue (University of Michigan)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I27837315","host_organization_name":"University of Michigan","host_organization_lineage":["https://openalex.org/I27837315"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W136106025.pdf","grobid_xml":"https://content.openalex.org/works/W136106025.grobid-xml"},"referenced_works_count":221,"referenced_works":["https://openalex.org/W4355260","https://openalex.org/W22627357","https://openalex.org/W32378874","https://openalex.org/W55364675","https://openalex.org/W107210068","https://openalex.org/W107671624","https://openalex.org/W111388456","https://openalex.org/W125106425","https://openalex.org/W136266878","https://openalex.org/W138814602","https://openalex.org/W149443649","https://openalex.org/W174418851","https://openalex.org/W184549435","https://openalex.org/W197615574","https://openalex.org/W310786876","https://openalex.org/W403527634","https://openalex.org/W602897313","https://openalex.org/W623607448","https://openalex.org/W1486344723","https://openalex.org/W1490172408","https://openalex.org/W1492587973","https://openalex.org/W1493251890","https://openalex.org/W1495977426","https://openalex.org/W1499739398","https://openalex.org/W1506642042","https://openalex.org/W1512072225","https://openalex.org/W1517494575","https://openalex.org/W1533444088","https://openalex.org/W1535874622","https://openalex.org/W1554671216","https://openalex.org/W1555642183","https://openalex.org/W1557686543","https://openalex.org/W1616649922","https://openalex.org/W1679032940","https://openalex.org/W1688621929","https://openalex.org/W1836073275","https://openalex.org/W1849819493","https://openalex.org/W1942214720","https://openalex.org/W1964013449","https://openalex.org/W1964302525","https://openalex.org/W1964538721","https://openalex.org/W1965027920","https://openalex.org/W1966176339","https://openalex.org/W1967637444","https://openalex.org/W1969690844","https://openalex.org/W1970445062","https://openalex.org/W1971615566","https://openalex.org/W1972144299","https://openalex.org/W1973957154","https://openalex.org/W1974383277","https://openalex.org/W1975153732","https://openalex.org/W1975449325","https://openalex.org/W1978542181","https://openalex.org/W1978640043","https://openalex.org/W1981809064","https://openalex.org/W1983482250","https://openalex.org/W1984279444","https://openalex.org/W1984909958","https://openalex.org/W1986091350","https://openalex.org/W1986320887","https://openalex.org/W1986785675","https://openalex.org/W1988518686","https://openalex.org/W1989722723","https://openalex.org/W1991315581","https://openalex.org/W1992637685","https://openalex.org/W1993236944","https://openalex.org/W1993470980","https://openalex.org/W1996180957","https://openalex.org/W1996981979","https://openalex.org/W1998422493","https://openalex.org/W1998423564","https://openalex.org/W1999671103","https://openalex.org/W2000043946","https://openalex.org/W2000529918","https://openalex.org/W2001735664","https://openalex.org/W2002154440","https://openalex.org/W2003386912","https://openalex.org/W2004206170","https://openalex.org/W2004877384","https://openalex.org/W2005441809","https://openalex.org/W2006999182","https://openalex.org/W2007127627","https://openalex.org/W2007495085","https://openalex.org/W2007625252","https://openalex.org/W2007796598","https://openalex.org/W2008181517","https://openalex.org/W2008945391","https://openalex.org/W2009183786","https://openalex.org/W2010298858","https://openalex.org/W2012173926","https://openalex.org/W2012295912","https://openalex.org/W2012655724","https://openalex.org/W2014196693","https://openalex.org/W2017178255","https://openalex.org/W2018077387","https://openalex.org/W2020321505","https://openalex.org/W2021192048","https://openalex.org/W2021548333","https://openalex.org/W2021590999","https://openalex.org/W2022135873","https://openalex.org/W2022803736","https://openalex.org/W2023817459","https://openalex.org/W2024105041","https://openalex.org/W2025522492","https://openalex.org/W2027526757","https://openalex.org/W2028350610","https://openalex.org/W2032351190","https://openalex.org/W2032417513","https://openalex.org/W2033107803","https://openalex.org/W2033968512","https://openalex.org/W2039048150","https://openalex.org/W2040370168","https://openalex.org/W2042409437","https://openalex.org/W2043141000","https://openalex.org/W2043921854","https://openalex.org/W2044117808","https://openalex.org/W2044744453","https://openalex.org/W2045114648","https://openalex.org/W2045309540","https://openalex.org/W2045850215","https://openalex.org/W2046369289","https://openalex.org/W2047263745","https://openalex.org/W2047571097","https://openalex.org/W2048428832","https://openalex.org/W2050810024","https://openalex.org/W2052286516","https://openalex.org/W2052352285","https://openalex.org/W2052564025","https://openalex.org/W2053308358","https://openalex.org/W2055592070","https://openalex.org/W2055946816","https://openalex.org/W2057315866","https://openalex.org/W2058617759","https://openalex.org/W2060945380","https://openalex.org/W2061174398","https://openalex.org/W2061561620","https://openalex.org/W2062853648","https://openalex.org/W2063495408","https://openalex.org/W2067038367","https://openalex.org/W2068146558","https://openalex.org/W2068382906","https://openalex.org/W2069800916","https://openalex.org/W2069990321","https://openalex.org/W2070228727","https://openalex.org/W2071348695","https://openalex.org/W2073974870","https://openalex.org/W2075761806","https://openalex.org/W2077340825","https://openalex.org/W2078374613","https://openalex.org/W2078532650","https://openalex.org/W2079226464","https://openalex.org/W2080916979","https://openalex.org/W2082480920","https://openalex.org/W2083579600","https://openalex.org/W2083883672","https://openalex.org/W2084092378","https://openalex.org/W2085418183","https://openalex.org/W2085602902","https://openalex.org/W2086141805","https://openalex.org/W2086493438","https://openalex.org/W2088762003","https://openalex.org/W2091396917","https://openalex.org/W2093359029","https://openalex.org/W2094061196","https://openalex.org/W2094334993","https://openalex.org/W2094985040","https://openalex.org/W2095453782","https://openalex.org/W2096628587","https://openalex.org/W2104954806","https://openalex.org/W2106107739","https://openalex.org/W2107535504","https://openalex.org/W2110224130","https://openalex.org/W2110252008","https://openalex.org/W2113999599","https://openalex.org/W2116176075","https://openalex.org/W2116609506","https://openalex.org/W2117820574","https://openalex.org/W2119158735","https://openalex.org/W2119683782","https://openalex.org/W2120021279","https://openalex.org/W2120492514","https://openalex.org/W2121693319","https://openalex.org/W2122028337","https://openalex.org/W2123123035","https://openalex.org/W2123555047","https://openalex.org/W2125715557","https://openalex.org/W2128016549","https://openalex.org/W2130361718","https://openalex.org/W2130866079","https://openalex.org/W2134844954","https://openalex.org/W2135603829","https://openalex.org/W2137577190","https://openalex.org/W2143339542","https://openalex.org/W2143938651","https://openalex.org/W2144701362","https://openalex.org/W2145662716","https://openalex.org/W2146226667","https://openalex.org/W2149967205","https://openalex.org/W2150048195","https://openalex.org/W2152683695","https://openalex.org/W2155783894","https://openalex.org/W2157226512","https://openalex.org/W2158882381","https://openalex.org/W2160029849","https://openalex.org/W2162586071","https://openalex.org/W2162653594","https://openalex.org/W2163861842","https://openalex.org/W2164173822","https://openalex.org/W2167490100","https://openalex.org/W2170507464","https://openalex.org/W2313419491","https://openalex.org/W2342079903","https://openalex.org/W2396560938","https://openalex.org/W2404433370","https://openalex.org/W2410623714","https://openalex.org/W2469240840","https://openalex.org/W2750896950","https://openalex.org/W2951102755","https://openalex.org/W2951245041","https://openalex.org/W2952538581","https://openalex.org/W2953327666"],"related_works":["https://openalex.org/W2985404048","https://openalex.org/W1966472904","https://openalex.org/W1989277510","https://openalex.org/W1900215118","https://openalex.org/W1553579855","https://openalex.org/W2580002043","https://openalex.org/W2080163983","https://openalex.org/W1948376788","https://openalex.org/W2884207463","https://openalex.org/W1975506525"],"abstract_inverted_index":{"The":[0,153,257,315],"resistance":[1],"of":[2,23,42,55,61,119,133,142,157,172,208,226,230,260,279,287,305,307,323],"tumor":[3,127,248],"cells":[4,46],"to":[5,162,191,198,237,266,284,300,347],"apoptosis":[6,43,68,125,252,310],"is":[7,81,138],"a":[8,38,49,59,163,179,206,290],"major":[9],"problem":[10],"in":[11,40,44,70,126,167,218,309,312],"current":[12],"cancer":[13,45,71,313],"therapies.":[14],"Successful":[15],"anticancer":[16],"strategies":[17],"would":[18],"benefit":[19],"from":[20,136],"specific":[21],"targeting":[22,31],"the":[24,28,32,67,116,168,202,223,285,302],"pathways":[25],"that":[26,36,318],"cause":[27],"resistance.":[29],"Hence,":[30],"crucial":[33],"negative":[34],"regulators":[35],"play":[37],"role":[39],"inhibition":[41],"might":[47],"be":[48],"promising":[50,291],"therapeutic":[51],"strategy.":[52],"IAPs":[53],"(Inhibitors":[54],"Apoptosis":[56],"Protein)":[57],"are":[58,264],"class":[60],"proteins":[62,176],"which":[63],"can":[64,177],"negatively":[65],"regulate":[66],"process":[69],"cells.":[72,128,314],"Among":[73],"eight":[74],"human":[75],"IAPs,":[76],"XIAP":[77,123,184],"(X-chromosome":[78],"linked":[79],"IAP)":[80],"most":[82],"potent":[83,270],"IAP":[84,97,146,151],"member":[85],"through":[86],"its":[87,94,104,329],"actions":[88],"on":[89,222,332,338],"both":[90,183,193,250],"caspase-9,":[91],"mediated":[92],"by":[93,343],"BIR":[95,108,111,169,185,188],"(Baculovirus":[96],"Repeat)":[98],"3":[99,170,186],"domain,":[100],"and":[101,110,148,187,195,210,216,253,328,334,336],"caspase-3/7":[102],"via":[103],"linker":[105],"region":[106],"between":[107],"1":[109],"2.":[112],"By":[113],"blocking":[114],"caspases,":[115],"central":[117],"executioners":[118],"programmed":[120],"cell":[121,255],"death,":[122],"inhibits":[124],"Smac":[129,159,175,212,231,241,262,275,281],"(Second":[130],"Mitochondria-derived":[131],"Activator":[132],"Caspase),":[134],"released":[135],"mitochondria,":[137],"an":[139],"endogenous":[140],"inhibitor":[141],"XIAP,":[143,238,327],"c-IAP1":[144,324,344],"(cellular":[145,150],"1),":[147],"c-IAP2":[149],"2).":[152],"amino-terminal":[154,224],"tetrapeptide":[155,225],"Ala-Val-Pro-Ile":[156],"mature":[158],"protein":[160],"binds":[161],"well-defined":[164],"surface":[165],"groove":[166],"domain":[171],"XIAP.":[173],"Moreover,":[174],"form":[178],"homodimer,":[180],"interacting":[181],"with":[182],"2":[189],"domains":[190],"release":[192],"initiator":[194],"effector":[196],"caspases":[197],"promote":[199],"apoptosis.":[200,348],"In":[201],"work":[203],"presented":[204],"here,":[205],"series":[207],"monvalent":[209],"bivalent":[211,261],"mimetics":[213,232,242,263,282],"were":[214],"designed":[215],"synthesized":[217],"this":[219],"dissertation,":[220],"based":[221],"Smac.":[227],"Both":[228],"types":[229],"show":[233,244,317],"high":[234],"binding":[235],"affinities":[236],"c-IAP1/2.":[239],"These":[240],"also":[243],"excellent":[245],"activity":[246,330],"against":[247],"cells,":[249],"inducing":[251],"inhibiting":[254],"growth.":[256],"cellular":[258,303],"activities":[259],"100":[265],"1000":[267],"times":[268],"more":[269],"than":[271],"their":[272],"corresponding":[273],"monovalent":[274,280],"variants.":[276],"Further":[277],"modifications":[278],"led":[283],"discovery":[286],"SM-406":[288,308,319],"as":[289],"drug":[292],"candidate.":[293],"Extensive":[294],"studies":[295,316],"have":[296],"been":[297],"carried":[298],"out":[299],"investigate":[301],"mechanism":[304],"action":[306],"induction":[311],"induces":[320],"rapid":[321],"degradation":[322,345],"but":[325],"not":[326],"depends":[331],"caspase-8":[333],"caspase-3":[335],"partially":[337],"caspase-9.":[339],"Caspase-8":[340],"activation":[341],"caused":[342],"leads":[346]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}