ArticleAntimicrobial agents and chemotherapy2015
A novel CDK7 inhibitor of the Pyrazolotriazine class exerts broad-spectrum antiviral activity at nanomolar concentrations.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 105 citations in OpenAlex.
- Assessment of combined antiviral drug treatment against selected α-, β-, and γ-herpesviruses.Virology journal · 2026Article
- New Assay Systems to Characterize the Broad-Spectrum Antiherpesviral and Non-Herpesviral Activity of Cyclin-Dependent Kinase (CDK) 8 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Dual targeting of CDK4/6 and CDK7 augments tumor response and antitumor immunity in breast cancer models.The Journal of clinical investigation · 2025Article
- Repurposing of CDK Inhibitors as Host Targeting Antivirals: A Mini- Review.Mini reviews in medicinal chemistry · 2025Review
- Cyclin Dependent Kinases in Antiviral Drug Discovery.Current medicinal chemistry · 2025Review
- CRL3Molecular cell · 2024Article
- Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7).European journal of medicinal chemistry · 2024Article
- Cyclin-Dependent Kinase 8 Represents a Positive Regulator of Cytomegalovirus Replication and a Novel Host Target for Antiviral Strategies.Pharmaceutics · 2024Article
- Review
- Design, Synthesis, and Biological Evaluation of 2,4-Diaminopyrimidine Derivatives as Potent CDK7 Inhibitors.ACS medicinal chemistry letters · 2024Article
- High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design.Nature communications · 2024Article
- Review
- An Antiherpesviral Host-Directed Strategy Based on CDK7 Covalently Binding Drugs: Target-Selective, Picomolar-Dose, Cross-Virus Reactivity.Pharmaceutics · 2024Article
- Current antiviral agents against human adenoviruses associated with respiratory infections.Frontiers in pediatrics · 2024Review
- Cryo-electron microscopy-based drug design.Frontiers in molecular biosciences · 2024Review
- Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers.Pharmaceutics · 2023Article
- Antiviral PROTACs: Opportunity borne with challenge.Cell insight · 2023Review
- Highly Conserved Interaction Profiles between Clinically Relevant Mutants of the Cytomegalovirus CDK-like Kinase pUL97 and Human Cyclins: Functional Significance of Cyclin H.International journal of molecular sciences · 2022Article
- Chemical inhibitors of transcription-associated kinases.Current opinion in chemical biology · 2022Review
- Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
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 in vitro in the nano-picomolar range. Novel data from a kinome-wide evaluation (>330 kinases profiled in vitro) 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 ± 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.