Bay 65-1942 hydrochloride is an ATP-competitive and selective inhibitor of IKKβ.

Administration of Bay 65-1942 before ischemia significantly reduces left ventricular infarct size compared to vehicle-treated animals, with observed reductions at all time points (prior to ischemia 42.7±4.1%, at reperfusion 42.7±7.5%, 2 hours of reperfusion 29.4±5.2%; each group P<0.05 vs. vehicle). Compared to sham animals, vehicle-treated animals show a significant increase in the infarct-to-area at risk (AAR) ratio (70.7±3.4 vs. 5.8±3.4%, P<0.05). Bay 65-1942 pretreatment (n=3) significantly lowers CK-MB levels compared to untreated animals prior to IR (14,170 ±3,219 units, P<0.05 vs. vehicle)[1].

AZD6244 and BAY 65-1942 demonstrate synergistic inhibition of cell viability at the dose combination (5 μM AZD6244+10 μM BAY 65-1942), which correlates with IC75 (CI?=?0.48±0.01). AZD6244 and BAY 65-1942 treatment induces 2- and 1.3-fold caspase 3/7 activation, respectively, compared to the DMSO-treated cells. Treatment with a combination of AZD6244 plus BAY 65-1942 leads to a 3.2-fold increase in caspase 3/7 activity[2]. Inhibitors of MEK (AZD6244) and IKK (BAY 65-1942) are used at their IC50 concentrations, as determined by a 48 hour MTS assay, which achieve sufficient inhibition of kinase activity. MYL-R cells are treated for 24 hours with AZD6244 (5 μM), BAY 65-1942 (10 μM), or a combination of these inhibitors at the same concentrations. Synergism is also indicated at the IC50 (CI?=?0.56±0.09) and IC90 (CI?=?0.46±0.02) dose combinations reported by the software (CI values are the mean of three independent experiments, ± standard deviation).