What question did this study set out to answer?

To design and characterize small-molecule inhibitors targeting EBNA1 DNA binding to suppress Epstein-Barr virus latent infection and EBV-driven tumorigenesis.

March 6, 2019Science Translational MedicineOpen Access

Structure-based design of small-molecule inhibitors of EBNA1 DNA binding blocks Epstein-Barr virus latent infection and tumor growth

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Authors

TMTroy E. MessickThe Wistar Institute GSGarry R. SmithFox Chase Chemical Diversity Center SSSamantha S. SoldanThe Wistar Institute

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Implication

Preclinical study demonstrates selective EBNA1 inhibition suppresses tumor growth in EBV-dependent cancer xenografts, highlighting a targeted therapeutic strategy for EBV-driven malignancies.

Key Points

To design and characterize small-molecule inhibitors targeting EBNA1 DNA binding to suppress Epstein-Barr virus latent infection and EBV-driven tumorigenesis.
Identified a 2,3-disubstituted benzoic acid inhibitor series using a fragment-based approach and X-ray crystallography.
Evaluated compound activity in vitro using biochemical assays, chromatin immunoprecipitation, and viral DNA replication assays.
Assessed in vivo therapeutic efficacy and tumor transcription effects across EBV-dependent xenografts, including patient-derived xenografts for nasopharyngeal carcinoma.
Inhibitors selectively blocked EBNA1 DNA-binding activity, viral replication, and EBV gene transcription in cell-based assays.
Treatment suppressed tumor growth across multiple EBV-dependent xenograft models, including nasopharyngeal carcinoma patient-derived xenografts.
Compounds altered cellular transforming growth factor-β (TGF-β) pathway signaling in tumor xenografts while exhibiting favorable pharmacological properties.

Cite This Study

Messick et al. (2019) studied this question.

synapsesocial.com/papers/69deab127702a00918b0c5cd https://doi.org/10.1126/scitranslmed.aau5612

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Implication

Preclinical study demonstrates selective EBNA1 inhibition suppresses tumor growth in EBV-dependent cancer xenografts, highlighting a targeted therapeutic strategy for EBV-driven malignancies.

Structure-based design of small-molecule inhibitors of EBNA1 DNA binding blocks Epstein-Barr virus latent infection and tumor growth

Discussion

Member takes

Implication

Key Points

Cite This Study

Structure-based design of small-molecule inhibitors of EBNA1 DNA binding blocks Epstein-Barr virus latent infection and tumor growth

Discussion

Member takes

Implication

Key Points

Cite This Study

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