{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:23:22Z","timestamp":1792513402539,"version":"4.5.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Protein kinases represent central and multifunctional regulators of a balanced virus-host interaction. Cyclin-dependent protein kinase 7 (CDK7) plays crucial regulatory roles in cell cycle and transcription, both connected with the replication of many viruses. Previously, we developed a CDK7 inhibitor, LDC4297, that inhibits CDK7\n            <jats:italic>in vitro<\/jats:italic>\n            in the nano-picomolar range. Novel data from a kinome-wide evaluation (&gt;330 kinases profiled\n            <jats:italic>in vitro<\/jats:italic>\n            ) demonstrate a kinase selectivity. Importantly, we provide first evidence for the antiviral potential of the CDK7 inhibitor LDC4297, i.e., in exerting a block of the replication of human cytomegalovirus (HCMV) in primary human fibroblasts at nanomolar concentrations (50% effective concentration, 24.5 \u00b1 1.3 nM). As a unique feature compared to approved antiherpesviral drugs, inhibition occurred already at the immediate-early level of HCMV gene expression. The mode of antiviral action was considered multifaceted since CDK7-regulated cellular factors that are supportive of HCMV replication were substantially affected by the inhibitors. An effect of LDC4297 was identified in the interference with HCMV-driven inactivation of retinoblastoma protein (Rb), a regulatory step generally considered a hallmark of herpesviral replication. In line with this finding, a broad inhibitory activity of the drug could be demonstrated against a selection of human and animal herpesviruses and adenoviruses, whereas other viruses only showed intermediate drug sensitivity. Summarized, the CDK7 inhibitor LDC4297 is a promising candidate for further antiviral drug development, possibly offering new options for a comprehensive approach to antiviral therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.04534-14","type":"journal-article","created":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T02:49:35Z","timestamp":1422326975000},"page":"2062-2071","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":106,"title":["A Novel CDK7 Inhibitor of the Pyrazolotriazine Class Exerts Broad-Spectrum Antiviral Activity at Nanomolar Concentrations"],"prefix":"10.1128","volume":"59","author":[{"given":"Corina","family":"Hutterer","sequence":"first","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Eickhoff","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Milbradt","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Korn","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Zeittr\u00e4ger","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanife","family":"Bahsi","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunther","family":"Zischinsky","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wolf","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Degenhart","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Unger","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Baumann","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Klebl","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Marschall","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"244","DOI":"10.2741\/Bregman","article-title":"Cell cycle regulation and RNA polymerase II","volume":"5","author":"Bregman DB","year":"2000","unstructured":"Bregman DB, Pestell RG, Kidd VJ. 2000. 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