| Autor: |
Lars Pache, Matthew D. Marsden, Peter Teriete, Alex J. Portillo, Dominik Heimann, Jocelyn T. Kim, Mohamed S.A. Soliman, Melanie Dimapasoc, Camille Carmona, Maria Celeridad, Adam M. Spivak, Vicente Planelles, Nicholas D.P. Cosford, Jerome A. Zack, Sumit K. Chanda |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Cell Reports Medicine, Vol 1, Iss 3, Pp 100037- (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2666-3791 |
| DOI: |
10.1016/j.xcrm.2020.100037 |
| Popis: |
Summary: “Shock and kill” strategies focus on purging the latent HIV-1 reservoir by treating infected individuals with therapeutics that activate the latent virus and subsequently eliminating infected cells. We have previously reported that induction of non-canonical nuclear factor κB (NF-κB) signaling through a class of small-molecule antagonists known as Smac mimetics can reverse HIV-1 latency. Here, we describe the development of Ciapavir (SBI-0953294), a molecule specifically optimized for HIV-1 latency reversal that was found to be more efficacious as a latency-reversing agent than other Smac mimetics under clinical development for cancer. Critically, this molecule induced activation of HIV-1 reservoirs in vivo in a bone marrow, liver, thymus (BLT) humanized mouse model without mediating systemic T cell activation. This study provides proof of concept for the in vivo efficacy and safety of Ciapavir and indicates that Smac mimetics can constitute a critical component of a safe and efficacious treatment strategy to eliminate the latent HIV-1 reservoir. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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