ZL0580

ZL0580, a structurally close analog of ZL0590, induces epigenetic suppression of HIV via selectively binding to BD1 domain of BRD4. ZL0580 induces HIV suppression by inhibiting Tat transactivation and transcription elongation as well as by inducing repressive chromatin structure at the HIV promoter[1][2][3].

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Infection

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

BRD4 (BD1)

ZL0580 (8 μM, 2 days, PBMCs of viremic HIV-infected individuals) induces HIV transcriptional suppression with low toxicity[1]. ZL0580 treatment (10 μM) suppresses both PMA-stimulated and basal HIV transcription[1]. Cell Viability Assay[1] Cell Line: HIV-infected human CD4+ T cells. Concentration: 0-8 μM. Incubation Time: 2 days. Result: Suppress HIV in primary CD4+ T cell. Single treatment (8 μM) led to almost completed loss of productive HIV infection in CD4+ T cells. RT-PCR[1] Cell Line: PBMCs of viremic HIV-infected individuals. Concentration: 8 μM. Incubation Time: 2 days. Result: Suppresses HIV transcription ex vivo in PBMCs of viremic HIV-infected individuals. Cell Cytotoxicity Assay[1] Cell Line: J-Lat cells. Concentration: 0-80 μM. Incubation Time: 1 and 3 days. Result: Did not cause significant cell death at concentrations below 40 μM. Treatment of J-Lat cells with ZL0580 (10 μM) also did not cause significant cell death on days 2, 7, and 14 compared with NC in both PMA-activated and unstimulated cells.

[1]. Niu Q, et al. Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV. J Clin Invest. 2019 Jul 22;129(8):3361-3373.

[2]. Vansant G, et al. Block-And-Lock Strategies to Cure HIV Infection. Viruses. 2020 Jan 10;12(1). pii: E84.

[3]. Brasier AR, et al. Validation of the epigenetic reader bromodomain-containing protein 4 (BRD4) as a therapeutic target for treatment of airway remodeling. Drug Discov Today. 2020 Jan;25(1):126-132.