Methods and Compositions for Re-activating Epstein-Barr Virus and Screening Compounds Therefor

摘要

In an effort to discover therapies for treating diseases caused by EBV, a novel screening assay for identifying compounds that reactivate EBV latent infection and a family of small molecules based on a tetrahydrocarboline backbone were discovered. Specifically, the compounds have the structure of the formula (I), wherein R1-R11 are defined herein and activate/reactivate EBV in a variety of cell types in a patient and are, therefore, useful in preventing or treating EBV-positive cancer, optionally with an anti-viral agent. In screening these compounds, novel compositions, EBV-positive cell lines, and methods are provided. (Formula I);

主权项

1. A method for activating Epstein-Barr virus (EBV), said method comprising administering a compound of formula (I) to a subject in need thereof: wherein:
R1 is H, C1 to C6 alkyl, C1 to C6 alkoxy, or halogen;R2 is H, C1 to C6 alkyl, or C1 to C6 alkoxy;R3 is optionally substituted aryl or heteroaryl;R4 is H or optionally substituted C1 to C6 alkyl;R5 to R11 are, independently, selected from the group consisting of H and C1 to C6 alkyl;R12 is H, C(O)OR3, C(O)NR3R4, or SO2R3; andis H, optionally substituted aryl, or optionally substituted heteroaryl; or a pharmaceutically acceptable acid salt or base salt or prodrug thereof.