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Table 1 HIV-1 latency reversal agents in various phases of HIV-1 therapeutic development

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

[81, 87]

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

[58, 135]

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

[138, 139]

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

[58, 141]

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

[49, 139]

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

[59, 142]

Scriptaid

HDAC inhibitor

J89GFP and A7 cells

Promotes hyperacetylation of histone

In vitro

[59, 143]

Givinostat (ITF2357 )

HDAC inhibitor

J89GFP, ACH2 and U1 cells

Induces hyperacetylation of histone

In vitro

[59, 144]

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

[64, 92, 93]

BIX-01294

HMT inhibitor

ACH-2 and OM10.1 cells

A G9a inhibitor, promotes repressive H3K9me2

Ex vivo

[64, 93]

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

[146, 147]

Phorbolmyristate acetate (PMA)

PKC agonist

J-Lat cell lines

 Activates NF-KB

Ex vivo

[146, 147]

Diterpene ester ingenol-3-angelate

PKC agonist

U1 cells

  Activates NF-KB

In vitro

[148]

Bryostatin-2

PKC agonist

CD4+ T-cells, J-Lat cell lines, U1 and OM10.1 cells

  Activates NF-KB

In vitro, ex vivo

[149, 150]

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

[109, 111]

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

[113–115]