{"id":"https://openalex.org/W2000953906","doi":"https://doi.org/10.1515/bc.2008.009","title":"A counterintuitive approach to treat enzyme deficiencies: use of enzyme inhibitors for restoring mutant enzyme activity","display_name":"A counterintuitive approach to treat enzyme deficiencies: use of enzyme inhibitors for restoring mutant enzyme activity","publication_year":2007,"publication_date":"2007-12-20","ids":{"openalex":"https://openalex.org/W2000953906","doi":"https://doi.org/10.1515/bc.2008.009","mag":"2000953906","pmid":"https://pubmed.ncbi.nlm.nih.gov/18095864"},"language":"en","primary_location":{"id":"doi:10.1515/bc.2008.009","doi":"https://doi.org/10.1515/bc.2008.009","is_oa":false,"landing_page_url":"https://doi.org/10.1515/bc.2008.009","pdf_url":null,"source":{"id":"https://openalex.org/S18118477","display_name":"Biological Chemistry","issn_l":"1431-6730","issn":["1431-6730","1437-4315"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-70","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310313990","host_organization_name":"De Gruyter","host_organization_lineage":["https://openalex.org/P4310313990"],"host_organization_lineage_names":["De Gruyter"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bchm","raw_type":"journal-article"},"volume":null,"type":"review","is_traditional":true,"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/A5102137255","display_name":"Jianqiang Fan","orcid":"https://orcid.org/0009-0005-1933-9500","observed_orcids":["https://orcid.org/0009-0005-1933-9500"]},"institutions":[{"id":"https://openalex.org/I98704320","display_name":"Icahn School of Medicine at Mount Sinai","ror":"https://ror.org/04a9tmd77","country_code":"US","type":"education","lineage":["https://openalex.org/I1320796813","https://openalex.org/I98704320"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jian-Qiang Fan","raw_affiliation_strings":["Department of Human Genetics, Mount Sinai School of Medicine, Fifth Avenue at 100th Street, New York, NY 10029, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Human Genetics, Mount Sinai School of Medicine, Fifth Avenue at 100th Street, New York, NY 10029, USA","institution_ids":["https://openalex.org/I98704320"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5102137255"],"corresponding_institution_ids":["https://openalex.org/I98704320"],"apc_list":{"value":0,"currency":"EUR","value_usd":0},"apc_paid":null,"fwci":1.5123,"has_fulltext":false,"cited_by_count":158,"citation_normalized_percentile":{"value":0.78688525,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":100},"biblio":{"volume":"389","issue":"1","first_page":"1","last_page":"11"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10945","display_name":"Lysosomal Storage Disorders Research","score":0.9916999936103821,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics (clinical)"},"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/T10945","display_name":"Lysosomal Storage Disorders Research","score":0.9916999936103821,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics (clinical)"},"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/T10934","display_name":"Heat shock proteins research","score":0.005499999970197678,"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/T12604","display_name":"Glycogen Storage Diseases and Myoclonus","score":0.001500000013038516,"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/pharmacological-chaperone-therapy","display_name":"pharmacological chaperone therapy","score":0.968999981880188},{"id":"https://openalex.org/keywords/competitive-inhibitors","display_name":"competitive inhibitors","score":0.8320000171661377},{"id":"https://openalex.org/keywords/lysosomal-storage-disorders","display_name":"lysosomal storage disease","score":0.8429999947547913},{"id":"https://openalex.org/keywords/protein-misfolding","display_name":"protein misfolding","score":0.8939999938011169},{"id":"https://openalex.org/keywords/er-associated-degradation","display_name":"ER-associated degradation","score":0.8460000157356262},{"id":"https://openalex.org/keywords/endoplasmic-reticulum","display_name":"endoplasmic reticulum","score":0.8199999928474426},{"id":"https://openalex.org/keywords/enzyme-deficiency","display_name":"enzyme deficiency","score":0.5379999876022339},{"id":"https://openalex.org/keywords/subinhibitory-concentrations","display_name":"subinhibitory concentrations","score":0.796999990940094},{"id":"https://openalex.org/keywords/small-molecule-drug-design","display_name":"small-molecule drug design","score":0.5649999976158142},{"id":"https://openalex.org/keywords/inborn-errors-of-metabolism","display_name":"inborn errors of metabolism","score":0.5040000081062317}],"concepts":[{"id":"https://openalex.org/C158619295","wikidata":"https://www.wikidata.org/wiki/Q21101062","display_name":"Endoplasmic-reticulum-associated protein degradation","level":4,"score":0.7903873920440674},{"id":"https://openalex.org/C61397870","wikidata":"https://www.wikidata.org/wiki/Q1069458","display_name":"Chemical chaperone","level":4,"score":0.7442970871925354},{"id":"https://openalex.org/C158617107","wikidata":"https://www.wikidata.org/wiki/Q79927","display_name":"Endoplasmic reticulum","level":2,"score":0.6366713047027588},{"id":"https://openalex.org/C2775962898","wikidata":"https://www.wikidata.org/wiki/Q5073152","display_name":"Chaperone (clinical)","level":2,"score":0.6219437122344971},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.5712448358535767},{"id":"https://openalex.org/C204328495","wikidata":"https://www.wikidata.org/wiki/Q847556","display_name":"Protein folding","level":2,"score":0.53107088804245},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.5298473834991455},{"id":"https://openalex.org/C2779926675","wikidata":"https://www.wikidata.org/wiki/Q6943700","display_name":"Mutant protein","level":4,"score":0.44538936018943787},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4429689645767212},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.442913681268692},{"id":"https://openalex.org/C98924942","wikidata":"https://www.wikidata.org/wiki/Q16886584","display_name":"Foldase","level":5,"score":0.4389587640762329},{"id":"https://openalex.org/C139447449","wikidata":"https://www.wikidata.org/wiki/Q14633900","display_name":"Unfolded protein response","level":3,"score":0.4346466660499573},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.43063318729400635},{"id":"https://openalex.org/C147816474","wikidata":"https://www.wikidata.org/wiki/Q169525","display_name":"Protein engineering","level":3,"score":0.4187707304954529},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3736151456832886},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.10617685317993164},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C547475151","wikidata":"https://www.wikidata.org/wiki/Q25419","display_name":"Escherichia coli","level":3,"score":0.0},{"id":"https://openalex.org/C87190427","wikidata":"https://www.wikidata.org/wiki/Q14864994","display_name":"GroEL","level":4,"score":0.0},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001665","descriptor_name":"Binding Sites","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D004798","descriptor_name":"Enzymes","qualifier_ui":"Q000172","qualifier_name":"deficiency","is_major_topic":true},{"descriptor_ui":"D004798","descriptor_name":"Enzymes","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006028","descriptor_name":"Glycosphingolipids","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008661","descriptor_name":"Metabolism, Inborn Errors","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D008661","descriptor_name":"Metabolism, Inborn Errors","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":true},{"descriptor_ui":"D008661","descriptor_name":"Metabolism, Inborn Errors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D016464","descriptor_name":"Lysosomal Storage Diseases","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D016464","descriptor_name":"Lysosomal Storage Diseases","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":false},{"descriptor_ui":"D016464","descriptor_name":"Lysosomal Storage Diseases","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D017510","descriptor_name":"Protein Folding","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018832","descriptor_name":"Molecular Chaperones","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1515/bc.2008.009","doi":"https://doi.org/10.1515/bc.2008.009","is_oa":false,"landing_page_url":"https://doi.org/10.1515/bc.2008.009","pdf_url":null,"source":{"id":"https://openalex.org/S18118477","display_name":"Biological Chemistry","issn_l":"1431-6730","issn":["1431-6730","1437-4315"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-70","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310313990","host_organization_name":"De Gruyter","host_organization_lineage":["https://openalex.org/P4310313990"],"host_organization_lineage_names":["De Gruyter"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bchm","raw_type":"journal-article"},{"id":"pmid:18095864","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/18095864","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":"Biological chemistry","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320306230","display_name":"American Heart Association","ror":"https://ror.org/013kjyp64"},{"id":"https://openalex.org/F4320311371","display_name":"Mizutani Foundation for Glycoscience","ror":"https://ror.org/052ywng59"},{"id":"https://openalex.org/F4320315747","display_name":"Amicus Therapeutics","ror":"https://ror.org/0328xw886"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":64,"referenced_works":["https://openalex.org/W36849100","https://openalex.org/W57809147","https://openalex.org/W1520171546","https://openalex.org/W1527172969","https://openalex.org/W1544162036","https://openalex.org/W1597854169","https://openalex.org/W1758125525","https://openalex.org/W1831130622","https://openalex.org/W1940027108","https://openalex.org/W1965705234","https://openalex.org/W1970041427","https://openalex.org/W1985609587","https://openalex.org/W1988511393","https://openalex.org/W1991019141","https://openalex.org/W1991103963","https://openalex.org/W1991968375","https://openalex.org/W1992335263","https://openalex.org/W1994334199","https://openalex.org/W1995538237","https://openalex.org/W1997278734","https://openalex.org/W2009725600","https://openalex.org/W2011709758","https://openalex.org/W2023397454","https://openalex.org/W2026507072","https://openalex.org/W2037010661","https://openalex.org/W2040321992","https://openalex.org/W2043591708","https://openalex.org/W2045893780","https://openalex.org/W2045955616","https://openalex.org/W2048168961","https://openalex.org/W2055349784","https://openalex.org/W2057261483","https://openalex.org/W2060496255","https://openalex.org/W2061614901","https://openalex.org/W2063240158","https://openalex.org/W2064752765","https://openalex.org/W2066472801","https://openalex.org/W2080299613","https://openalex.org/W2089271373","https://openalex.org/W2093722439","https://openalex.org/W2095446380","https://openalex.org/W2096328095","https://openalex.org/W2096966529","https://openalex.org/W2104078095","https://openalex.org/W2111013904","https://openalex.org/W2112126380","https://openalex.org/W2117143712","https://openalex.org/W2124305857","https://openalex.org/W2124663723","https://openalex.org/W2132823811","https://openalex.org/W2135424735","https://openalex.org/W2147001430","https://openalex.org/W2149369491","https://openalex.org/W2151653841","https://openalex.org/W2159823307","https://openalex.org/W2160928326","https://openalex.org/W2163130181","https://openalex.org/W2167159839","https://openalex.org/W2169690599","https://openalex.org/W2171406737","https://openalex.org/W2333536387","https://openalex.org/W2334691957","https://openalex.org/W2341701597","https://openalex.org/W3205141978"],"related_works":["https://openalex.org/W2011709758","https://openalex.org/W1914553089","https://openalex.org/W1981632300","https://openalex.org/W2020895861","https://openalex.org/W3046165406","https://openalex.org/W7220773051","https://openalex.org/W2080494254","https://openalex.org/W2116313758","https://openalex.org/W2724981758","https://openalex.org/W2784044092"],"abstract_inverted_index":{"Pharmacological":[0],"chaperone":[1,170],"therapy":[2,171],"is":[3,187],"an":[4,160],"emerging":[5],"counterintuitive":[6],"approach":[7],"to":[8,36,86,104,107,111,139],"treat":[9,112,140],"protein":[10,17,38,150],"deficiencies":[11],"resulting":[12],"from":[13],"mutations":[14],"causing":[15],"misfolded":[16],"conformations.":[18],"Active-site-specific":[19],"chaperones":[20,29],"(ASSCs)":[21],"are":[22,73,90,96,118,123],"enzyme":[23,67,83,116],"active-site":[24],"directed":[25],"small":[26,99],"molecule":[27],"pharmacological":[28,169],"that":[30],"act":[31],"as":[32,79,152],"a":[33,49,141,153,177],"folding":[34,39],"template":[35],"assist":[37],"of":[40,53,82,144,162,168,185],"mutant":[41,54],"proteins":[42,55],"in":[43,56,156,165],"the":[44,57,80,166,173,181],"endoplasmic":[45],"reticulum":[46],"(ER).":[47],"As":[48],"result,":[50],"excessive":[51],"degradation":[52,59],"ER-associated":[58],"(ERAD)":[60],"machinery":[61],"can":[62],"be":[63],"prevented,":[64],"thus":[65],"restoring":[66],"activity.":[68],"Lysosomal":[69],"storage":[70,89],"disorders":[71],"(LSDs)":[72],"suitable":[74],"candidates":[75],"for":[76,135,172,180],"ASSC":[77],"treatment,":[78],"levels":[81],"activity":[84],"needed":[85],"prevent":[87],"substrate":[88],"relatively":[91],"low.":[92],"In":[93,175],"addition,":[94,176],"ASSCs":[95,120,186],"orally":[97],"active":[98],"molecules":[100],"and":[101,158,183],"have":[102],"potential":[103],"gain":[105],"access":[106],"most":[108],"cell":[109],"types":[110],"neuronopathic":[113],"LSDs.":[114],"Competitive":[115],"inhibitors":[117],"effective":[119],"when":[121],"they":[122],"used":[124],"at":[125],"sub-inhibitory":[126],"concentrations.":[127],"This":[128,147],"whole":[129],"new":[130],"paradigm":[131],"provides":[132,159],"excellent":[133],"opportunity":[134],"identifying":[136],"specific":[137],"drugs":[138],"broad":[142],"range":[143],"inherited":[145],"disorders.":[146],"review":[148],"describes":[149],"misfolding":[151],"pathophysiological":[154],"cause":[155],"LSDs":[157],"overview":[161],"recent":[163],"advances":[164],"development":[167],"diseases.":[174],"generalized":[178],"guidance":[179],"design":[182],"screening":[184],"also":[188],"presented.":[189]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":3},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":9},{"year":2020,"cited_by_count":5},{"year":2019,"cited_by_count":9},{"year":2018,"cited_by_count":5},{"year":2017,"cited_by_count":7},{"year":2016,"cited_by_count":5},{"year":2015,"cited_by_count":6},{"year":2014,"cited_by_count":14},{"year":2013,"cited_by_count":16},{"year":2012,"cited_by_count":16}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}