ZL0580 (ZL-0580) is a small molecule that induces epigenetic suppression of HIV via BRD4, suppresses PMA-induced HIV activation.
ZL0580 induces epigenetic reprogramming of HIV LTR in J-Lat cells, suppresses HIV in in vitro HIV-infected human CD4+ T cells, did not significantly alter HIV DNA levels, but reduced HIV transcription in PBMCs.
ZL0580 suppresses HIV transcription ex vivo in PBMCs of viremic HIV-infected participants.
ZL0580 more selectively binds to the BRD4 BD1 domain (IC50=163 nM) instead of BD2 (IC50=1071 nM).
ZL0580 also displays approximately 6- to 11-fold selectivity for BRD4 over other BET proteins (IC50 ranged from approximately 0.9 to 1.9 μM) as well as over a non-BET BD protein, CBP (IC50 >10 uM).
ZL0580 inhibits Tat transactivation and key factors in HIV transcription elongation.
