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

Administering Bay 65-1942 before ischemia significantly reduces the size of left ventricular infarcts compared to controls given a placebo. This effect is evident at every measured interval, with notable reductions in the infarct-to-area-at-risk (AAR) ratio when Bay 65-1942 is administered before ischemia, at reperfusion, and after 2 hours of reperfusion, showing significant differences when compared with the placebo group (P<0.05 for each comparison). Furthermore, animals pretreated with Bay 65-1942 exhibited substantially lower creatine kinase-MB (CK-MB) levels, indicating less cardiac muscle damage, compared to those not receiving the compound prior to ischemia-reperfusion (IR), highlighting its protective role against heart tissue damage (P<0.05 vs. placebo).

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).