Methods and Compositions for Re-activating Epstein-Barr Virus and Screening Compounds Therefor
AssigneesThe Wistar Institute of Anatomy and Biology, Drexel University
InventorsPaul M. Lieberman, Nadezhda Tikhmyanova-Eckert, Joseph M. Salvino
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Abstract
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.
Claims16
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt or prodrug thereof.
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;
- and
- R13 is H, optionally substituted aryl, or optionally substituted heteroaryl;
- or a pharmaceutically acceptable salt or prodrug thereof.
A kit comprising:
- an anti-viral agent;
- and
- a compound of formula (I):
- 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;
- and
- R13 is H, optionally substituted aryl, or optionally substituted heteroaryl;
- or a pharmaceutically acceptable salt or prodrug thereof.
Dependencies are inferred from the claim text.