ArticleAntimicrobial agents and chemotherapy2004
Novel chemical class of pUL97 protein kinase-specific inhibitors with strong anticytomegaloviral activity.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 141 citations in OpenAlex.
- 'Getting Better'-Is It a Feasible Strategy of Broad Pan-Antiherpesviral Drug Targeting by Using the Nuclear Egress-Directed Mechanism?International journal of molecular sciences · 2024Review
- Article
- Cyclin-Dependent Kinases (CDKs) and the Human Cytomegalovirus-Encoded CDK Ortholog pUL97 Represent Highly Attractive Targets for Synergistic Drug Combinations.International journal of molecular sciences · 2022Article
- Acid-Catalyzed Synthesis of Isatoic Anhydride-8-Secondary Amides Enables IASA Transformations for Medicinal Chemistry.The Journal of organic chemistry · 2022Article
- Host-Directed Antiviral Therapy.Clinical microbiology reviews · 2020Review
- The Cytomegalovirus Protein Kinase pUL97:Host Interactions, Regulatory Mechanisms and Antiviral Drug Targeting.Microorganisms · 2020Review
- Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy.Current hematologic malignancy reports · 2020Review
- Article
- Role of MAPK/MNK1 signaling in virus replication.Virus research · 2018Review
- Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities againstACS omega · 2017Article
- Article
- The Interaction between Cyclin B1 and Cytomegalovirus Protein Kinase pUL97 is Determined by an Active Kinase Domain.Viruses · 2015Article
- The proteome of human cytomegalovirus virions and dense bodies is conserved across different strains.Medical microbiology and immunology · 2015Article
- Differential properties of cytomegalovirus pUL97 kinase isoforms affect viral replication and maribavir susceptibility.Journal of virology · 2014Article
- A new synthetic route to original sulfonamide derivatives in 2-trichloromethylquinazoline series: a structure-activity relationship study of antiplasmodial activity.Molecules (Basel, Switzerland) · 2012Article
- Cytomegalovirus antivirals and development of improved animal models.Expert opinion on drug metabolism & toxicology · 2011Review
- The search for new therapies for human cytomegalovirus infections.Virus research · 2011Review
- Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir.Reviews in medical virology · 2009Review
- Cyclin-dependent Kinases Phosphorylate the Cytomegalovirus RNA Export Protein pUL69 and Modulate Its Nuclear Localization and Activity.The Journal of biological chemistry · 2009Article
- Conserved herpesvirus protein kinases.Biochimica et biophysica acta · 2008Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) is a major human pathogen frequently associated with life-threatening disease in immunosuppressed patients and newborns. The HCMV UL97-encoded protein kinase (pUL97) represents an important determinant of viral replication. Recent studies demonstrated that pUL97-specific kinase inhibitors are powerful tools for the control of HCMV replication. We present evidence that three related quinazoline compounds are potent inhibitors of the pUL97 kinase activity and block in vitro substrate phosphorylation, with 50% inhibitory concentrations (IC(50)s) between 30 and 170 nM. Replication of HCMV in primary human fibroblasts was suppressed with a high efficiency. The IC(50)s of these three quinazoline compounds (2.4 +/- 0.4, 3.4 +/- 0.6, and 3.9 +/- 1.1 microM, respectively) were in the range of the IC(50) of ganciclovir (1.2 +/- 0.2 microM), as determined by the HCMV green fluorescent protein-based antiviral assay. Importantly, the quinazolines were demonstrated to have strong inhibitory effects against clinical HCMV isolates, including ganciclovir- and cidofovir-resistant virus variants. Moreover, in contrast to ganciclovir, the formation of resistance to the quinazolines was not observed. The mechanisms of action of these compounds were confirmed by kinetic analyses with infected cells. Quinazolines specifically inhibited viral early-late protein synthesis but had no effects at other stages of the replication cycle, such as viral entry, consistent with a blockage of the pUL97 function. In contrast to epithelial growth factor receptor inhibitors, quinazolines affected HCMV replication even when they were added hours after virus adsorption. Thus, our findings indicate that quinazolines are highly efficient inhibitors of HCMV replication in vitro by targeting pUL97 protein kinase activity.
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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.