From: Epigenetic control of HIV-1 post integration latency: implications for therapy
Latency reversal agent | Class of agent | Agent tested on | Mechanism of action | Stage of therapeutic development | Ref |
---|---|---|---|---|---|
Vorinostat (SAHA) | HDAC inhibitor | J89 cells and Resting CD4+ T cells | Induce acetylation of histone H3K4, H4K4 resulting in remodeling of nuc-1 | In vitro, ex vivo and tested in a clinical trial | |
Valproic acid | HDAC inhibitor | J-Lat cell lines and U1 cells, patient derived cells | Formation of euchromatin at HIV-1 5′LTR and reactivation of HIV-1 transcription | In vitro, ex vivo, and tested in a clinical trial | |
Panobinostat | HDAC inhibitor | CD4+ T cells | Formation of euchromatin at HIV-1 5′LTR and reactivation of HIV-1 transcription | Phase 1/2 clinical trial | [136] |
Romidepsin | HDAC inhibitor | CD4+ T cells | Formation of euchromatin at HIV-1 5′LTR and reactivation of HIV-1 transcription | Ex vivo | [137] |
Entinostat | HDAC inhibitor | CD4+ T cells, ACH2, and J-lat cell lines | Formation of euchromatin at HIV-1 5′LTR and reactivation of HIV-1 transcription | In vitro, ex vivo | |
M344 | HDAC inhibitor | J-Lat clones (A7) | Increases histone acetylation and activation of NF-kappaB | In vitro | [140] |
Sodium butyrate | HDAC inhibitor | CD4+ T cells, J-Lat cell lines, ACH2 and U1 cells | Increases histone acetylation resulting in transcriptional activation of HIV-1 promoter | In vitro | |
Trichostatin A | HDAC inhibitor | CD4+ T cells, ACH2, and J49 cells |  Increases histone acetylation resulting in transcriptional activation of HIV-1 promoter | In vitro, ex vivo | |
Oxamflatin | HDAC inhibitor | J89GFP and A7 cell | Increases the acetylation level of histone H3 and histone H4 at the nucleosome 1(nuc-1) site | In vitro | |
Scriptaid | HDAC inhibitor | J89GFP and A7 cells | Promotes hyperacetylation of histone | In vitro | |
Givinostat (ITF2357 ) | HDAC inhibitor | J89GFP, ACH2 and U1 cells | Induces hyperacetylation of histone | In vitro | |
CG05/CG06 | HDAC inhibitor | ACH2 cells | Induces hyperacetylation of histone | In vitro | [145] |
Chaetocin | HMT inhibitor | Resting CD4+ T cells isolated from HIV infected patients, ACH-2, OM10.1 cells, infected Jurkat-tat cells | A Suv39H1 inhibitor, induces loss of H3K9me3 | In vitro, ex vivo | |
BIX-01294 | HMT inhibitor | ACH-2 and OM10.1 cells | A G9a inhibitor, promotes repressive H3K9me2 | Ex vivo | |
3-deazaneplanocin A | HMT inhibitor | Latently infected Jurkat E4 and G4 cells | An inhibitor of EZH2, Induces loss of H3K27me3 | In vitro | [65] |
5-aza-2′deoxycytidine | DNMTI | ACH-2 cells, U1 cells, and J-Lat cell lines | Inhibits of cytosine methylation and prevent the recruitment of MBD2 and HDAC2 to the 5′LTR | In vitro | [97] |
Prostratin | PKC agonist | Patient derived CD4 + T cells, J-Lat cell lines | Activates NF-KB | Ex vivo | |
Phorbolmyristate acetate (PMA) | PKC agonist | J-Lat cell lines | Â Activates NF-KB | Ex vivo | |
Diterpene ester ingenol-3-angelate | PKC agonist | U1 cells | Â Â Activates NF-KB | In vitro | [148] |
Bryostatin-2 | PKC agonist | CD4+ T-cells, J-Lat cell lines, U1 and OM10.1 cells | Â Â Activates NF-KB | In vitro, ex vivo | |
JQ1 | Unclassified agents | CD4+ T cells derived from patient, J-Lat cell lines, U1, ACH2, and OM10.1 cells | Releases BRD4 from the 5′LTR and allows Tat-mediated recruitment of P-TEFb to the 5′LTR. | In vitro and ex vivo | |
I-Bet, I-Bet151 and MS417 | Unclassified agents | J-Lat cell lines, primary CD4+ T cells |  Releases BRD4 from the 5′LTR and allows Tat-mediated recruitment of P-TEFb to the 5′LTR. | In vitro | [111] |
Disulfiram | Unclassified agents | CD4+ T cells | Reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. | Ex vivo, clinical trial |