The thioacetate-ω(γ-lactam carboxamide) HDAC inhibitor ST7612AA1 as HIV-1 latency reactivation agent

Antiviral Research
Roger BadiaJosé A Esté

Abstract

Antiretroviral therapy (ART) is unable to cure HIV infection. The ability of HIV to establish a subset of latent infected CD4(+) T cells, which remain undetectable to the immune system, becomes a major roadblock to achieve viral eradication. Histone deacetylase inhibitors (HDACi) have been shown to potently induce the reactivation of latent HIV. Here, we show that a new thiol-based HDACi, the thioacetate-ω(γ-lactam carboxamide) derivative ST7612AA1, is a potent inducer of HIV reactivation. We evaluated HIV reactivation activity of ST7612AA1 compared to panobinostat (PNB), romidepsin (RMD) and vorinostat (VOR) in cell culture models of HIV-1 latency, in latently infected primary CD4(+) T lymphocytes and in PBMCs from HIV(+) patients. ST7612AA1 potently induced HIV-1 reactivation at submicromolar concentrations with comparable potency to panobinostat or superior to vorinostat. The presence of known antiretrovirals did not affect ST7612AA1-induced reactivation and their activity was not affected by ST7612AA1. Cell proliferation and cell activation were not affected by ST7612AA1, or any other HDACi used. In conclusion, our results indicate that ST7612AA1 is a potent activator of latent HIV and that reactivation activity of ST7612AA...Continue Reading

References

Jan 10, 2008·Molecular Pharmacology·Gemma MoncunillJosé A Esté
Oct 8, 2009·Antiviral Research·Viktor DahlSarah Palmer
Oct 26, 2010·Methods : a Companion to Methods in Enzymology·Alberto Bosque, Vicente Planelles
Mar 5, 2013·Current Opinion in HIV and AIDS·Ronald Mitsuyasu
Mar 29, 2013·Journal of Virology·Liang ShanRobert F Siliciano
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Anthony R CilloJohn W Mellors
Aug 20, 2014·PloS One·Kirston M BartonDavid M Margolis
Mar 10, 2015·Trends in Microbiology·Katherine M BrunerRobert F Siliciano
Mar 31, 2015·The Journal of Clinical Investigation·Gregory M LairdRobert F Siliciano
Jun 2, 2015·Acta Pharmacologica Sinica·Hong-tao ShangFu-jun Liang

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Citations

Nov 7, 2015·The Journal of Antimicrobial Chemotherapy·Roger BadiaJosé A Esté
Apr 1, 2017·Antiviral Research·Roger BadiaEva Riveira-Muñoz
Sep 7, 2017·Antimicrobial Agents and Chemotherapy·Edurne Garcia-VidalJosé A Esté
Jan 13, 2021·Chemical Communications : Chem Comm·Claudio CianferottiGiuseppe Giannini
Feb 5, 2021·European Journal of Medicinal Chemistry·Juliana Romano LopesJean Leandro Dos Santos
Dec 12, 2018·Journal of Medicinal Chemistry·Maxim B NawrozkijDante Rotili

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