Description
BI-7273 is a potent BRD9 bromodomain inhibitor (K
d = 15.4 nM; IC
50 = 19 nM) that less effectively inhibits the functionally and structurally related BRD7 bromodomain (IC
50 = 117 nM). It is without effect against the bromodomains of BRD2 and BRD4, as well as a panel of kinases. BI-7273 inhibits the growth of EOL-1 acute myeloid leukemia cells
in vitro (EC
50 = 1.4 μM).
in vitro
bi-7273 was previously demonstrated to mimic genetic perturbation of brd9. bi-7273 could also target brd7 bd, a bd protein that was found in a subclass of swi/snf remodelling complexes sharing high sequence homology with brd9. in addition, bi-7273 was able to form an additional positive interaction with the carbonyl of asn100 in brd9. furthermore, bi-7273 showed no measurable activity against bet family bds even up to a concentration of 100 μm in the biochemical alpha assay [1].
in vivo
in order to explore the potential of bi-7273 as in-vivo chemical probe, female bomtac:nmrifoxn1nu mice was orally administered two doses at 20 and 180 mg/ kg and the concentration of bi-7273 in plasma over time was measured. results showed that dose-dependent but nonlinear auc was observed for bi-7273, achieving exposure that was higher compared to the ec50 level determined for bi-7273 in proliferation assays with eol-1 cells [1].
IC 50
19 and 117 nm for brd9 and brd7, respectively.
References
[1] martin lj et al. structure-based design of an in vivo active selective brd9 inhibitor. j med chem.2016 may 26;59(10):4462-75.
