| Autor: |
Graci JD; PTC Therapeutics, Inc., South Plainfield, New Jersey, United States of America., Michaels D; Department of Medicine and Microbiology, Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, United States of America., Chen G; PTC Therapeutics, Inc., South Plainfield, New Jersey, United States of America., Schiralli Lester GM; Department of Pediatrics, Neonatology, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, New York, United States of America., Nodder S; Department of Medicine and Microbiology, Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, United States of America., Weetall M; PTC Therapeutics, Inc., South Plainfield, New Jersey, United States of America., Karp GM; PTC Therapeutics, Inc., South Plainfield, New Jersey, United States of America., Gu Z; PTC Therapeutics, Inc., South Plainfield, New Jersey, United States of America., Colacino JM; PTC Therapeutics, Inc., South Plainfield, New Jersey, United States of America., Henderson AJ; Department of Medicine and Microbiology, Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, United States of America. |
| Abstrakt: |
Despite advances in antiretroviral therapy, HIV-1 infection remains incurable in patients and continues to present a significant public health burden worldwide. While a number of factors contribute to persistent HIV-1 infection in patients, the presence of a stable, long-lived reservoir of latent provirus represents a significant hurdle in realizing an effective cure. One potential strategy to eliminate HIV-1 reservoirs in patients is reactivation of latent provirus with latency reversing agents in combination with antiretroviral therapy, a strategy termed "shock and kill". This strategy has shown limited clinical effectiveness thus far, potentially due to limitations of the few therapeutics currently available. We have identified a novel class of benzazole compounds effective at inducing HIV-1 expression in several cellular models. These compounds do not act via histone deacetylase inhibition or T cell activation, and show specificity in activating HIV-1 in vitro. Initial exploration of structure-activity relationships and pharmaceutical properties indicates that these compounds represent a potential scaffold for development of more potent HIV-1 latency reversing agents. |
