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S.L. Lim et al.
ARV 825 degrades bromodomain extraterminal domain proteins
We evaluated the ability of ARV 825 to degrade BRD 2, BRD 3 and BRD 4 proteins after KMS11 and KMS28BM cells were treated with 10 nM and 100 nM ARV 825, respectively, for either 2, 8, 24 or 48 h. In addition, after
treatment for 48 h, ARV 825 was washed out and BRD 2, BRD 3 and BRD 4 proteins were examined at 6 h, 24 h and 48 h post wash-out (Figure 3A). Lysates were analyzed by western blot. ARV 825 significantly degraded BRD 2 and BRD 4 by 2 h, but the effect on levels of BRD 3 protein was minimal. After wash-out in KMS11, BRD 2 returned
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Figure 6. Combination Index (CI) plot of MZ1 with small molecule inhibitors. Synergistic growth inhibi- tion of KMS11 and KMS28BM multiple myeloma cells in the presence of MZ1 and small molecule inhibitors as measured by MTT assay. CI defines interaction between MZ1 and small molecule inhibitor as plotted against a fraction of cell viability. CI<1, CI=1, and CI>1 represent synergism, additive, and antagonism of the two compounds, respective- ly. Values of CI analysis are shown in Online Supplementary Table S4.
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haematologica | 2019; 104(6)