SKLB-39b is a potent, selective BET bromodomain 1 (BD1) inhibitor with IC50 of 42 nM for BRD4-BD1, with >100-fold BD2 selectivity, disrupts BRD4-BD1-p62 interaction and exhits antifibrotic effect.
inhibits fibroblast activation by inducing protective autophagy against NIH3T3cells with IC50 of 2.5 uM.
SKLB-39b markedly reduced α-SMA expression and its colocalization with BRD4 in activated fibroblasts.
SKLB-39b restores ULK1-dependent autophagy, inhibits TGF-β1-induced A549 cell migration more effectively than JQ1.
SKLB-39b exerts anti-fibrotic effects via reactivation of protective autophagy, promotes autophagosome-lysosome fusion and induces complete autophagic flux.
SKLB-39b shows selective binding BRD4-BD1 with BLI KD of 208 nM.
SKLB-39b (30 or 60 mg/kg, i.p.) improved survival in bleomycin-induced pulmonary fibrosis in mice model of bleomycin-induced pulmonary fibrosis.
SKLB-39b engages BRD4-BD1 through Leu92 and Ile146, weakens BRD4-BD1-p62 association, reduces p62 protein accumulation, and restores protective autophagy in activated fibroblasts.