{"?xml":{"@version":"1.0"},"edm:RDF":{"@xmlns:dc":"http://purl.org/dc/elements/1.1/","@xmlns:edm":"http://www.europeana.eu/schemas/edm/","@xmlns:wgs84_pos":"http://www.w3.org/2003/01/geo/wgs84_pos","@xmlns:foaf":"http://xmlns.com/foaf/0.1/","@xmlns:rdaGr2":"http://rdvocab.info/ElementsGr2","@xmlns:oai":"http://www.openarchives.org/OAI/2.0/","@xmlns:owl":"http://www.w3.org/2002/07/owl#","@xmlns:rdf":"http://www.w3.org/1999/02/22-rdf-syntax-ns#","@xmlns:ore":"http://www.openarchives.org/ore/terms/","@xmlns:skos":"http://www.w3.org/2004/02/skos/core#","@xmlns:dcterms":"http://purl.org/dc/terms/","edm:WebResource":[{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:doc-4NOQCX9Z/6447ab6f-04f1-4a45-9bf4-709cd4bdf3aa/PDF","dcterms:extent":"1335 KB"},{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:doc-4NOQCX9Z/42bc5c22-0ae8-4c7d-9e75-84c82b1825ec/TEXT","dcterms:extent":"0 KB"}],"edm:TimeSpan":{"@rdf:about":"2005-2025","edm:begin":{"@xml:lang":"en","#text":"2005"},"edm:end":{"@xml:lang":"en","#text":"2025"}},"edm:ProvidedCHO":{"@rdf:about":"URN:NBN:SI:doc-4NOQCX9Z","dcterms:isPartOf":[{"@rdf:resource":"https://www.dlib.si/details/URN:NBN:SI:spr-8ER5ZBJN"},{"@xml:lang":"sl","#text":"Farmacevtski vestnik"}],"dcterms:issued":"2021","dc:creator":["Anderluh, Marko","Bricelj, Aleša","Sosič, Izidor"],"dc:format":[{"@xml:lang":"sl","#text":"številka:2"},{"@xml:lang":"sl","#text":"letnik:72"},{"@xml:lang":"sl","#text":"str. 100-106"}],"dc:identifier":["ISSN:0014-8229","COBISSID_HOST:64793091","URN:URN:NBN:SI:doc-4NOQCX9Z"],"dc:language":"sl","dc:publisher":{"@xml:lang":"sl","#text":"Slovensko farmacevtsko društvo"},"dc:subject":[{"@xml:lang":"sl","#text":"Farmacevtska kemija"},{"@xml:lang":"sl","#text":"himerni razgrajevalci"},{"@xml:lang":"sl","#text":"ligaze E3"},{"@xml:lang":"sl","#text":"proteasom"},{"@xml:lang":"sl","#text":"razgradnja proteinov"}],"dcterms:temporal":{"@rdf:resource":"2005-2025"},"dc:title":{"@xml:lang":"sl","#text":"Tarčna razgradnja proteinov z uporabo himernih molekul| Utilizing proteolysis-targeting chimeras for targeted protein degradation|"},"dc:description":[{"@xml:lang":"sl","#text":"A novel approach using chimeric molecules that utilise the ubiquitin-proteasome system to induce proteolytic degradation of targeted proteins has been discovered recently. These bifunctional compounds are termed proteolysis-targeting chimeras or PROTACs and are comprised of three elements: a ligand for the E3 ligase, a ligand binding to the protein of interest and a linker connecting the two. The mechanism of action allows PROTACs to induce the degradation of a targeted protein in low concentrations and with high selectivity. This eventdriven pharmacological approach represents a better alternative to the occupancy-driven strategy, particularly in diseases, in which resistance to classical protein inhibitors or their compensatory overexpression often develop"},{"@xml:lang":"sl","#text":"V zadnjih letih se je razvoj himernih molekul, ki izkoriščajo ubikvitin-proteasomski sistem za proteolitično razgradnjo tarčnih proteinov, izkazal za izjemno obetaven pristop v farmacevtski kemiji. Tovrstne himerne razgrajevalce imenujemo molekule PROTAC (proteolysis-targeting chimeras), sestavljeni pa so iz treh delov: liganda za izbrano ubikvitin ligazo E3, ustreznega distančnika oz. vmesnika in liganda, ki se veže na tarčni protein. Zaradi svojega mehanizma delovanja lahko te molekule v nizkih koncentracijah in z visoko selektivnostjo dosežejo razgradnjo tarčnega proteina. Tovrsten farmakološki pristop se je že izkazal za boljšo alternativo klasičnemu farmakološkemu modelu zasedenosti receptorjev ali encimov predvsem pri patoloških stanjih, pri katerih se pogosto razvije odpornost na klasične zaviralce proteinov, bodisi zaradi kompenzatornega povečanja izražanja ali mutacije tarčnega proteina"}],"edm:type":"TEXT","dc:type":[{"@xml:lang":"sl","#text":"znanstveno časopisje"},{"@xml:lang":"en","#text":"journals"},{"@rdf:resource":"http://www.wikidata.org/entity/Q361785"}]},"ore:Aggregation":{"@rdf:about":"http://www.dlib.si/?URN=URN:NBN:SI:doc-4NOQCX9Z","edm:aggregatedCHO":{"@rdf:resource":"URN:NBN:SI:doc-4NOQCX9Z"},"edm:isShownBy":{"@rdf:resource":"http://www.dlib.si/stream/URN:NBN:SI:doc-4NOQCX9Z/6447ab6f-04f1-4a45-9bf4-709cd4bdf3aa/PDF"},"edm:rights":{"@rdf:resource":"http://rightsstatements.org/vocab/InC/1.0/"},"edm:provider":"Slovenian National E-content Aggregator","edm:intermediateProvider":{"@xml:lang":"en","#text":"National and University Library of Slovenia"},"edm:dataProvider":{"@xml:lang":"sl","#text":"Slovensko farmacevtsko društvo"},"edm:object":{"@rdf:resource":"http://www.dlib.si/streamdb/URN:NBN:SI:doc-4NOQCX9Z/maxi/edm"},"edm:isShownAt":{"@rdf:resource":"http://www.dlib.si/details/URN:NBN:SI:doc-4NOQCX9Z"}}}}