Bay 65-1942

Research use only, not for human use.

A potent, selective, ATP-competitive inhibitor of IKKβ kinase with Ki of 2 nM.

A potent, selective, ATP-competitive inhibitor of IKKβ kinase with Ki of 2 nM; dispalys >50-fold selectivity over IKK-α, does not inhibit (IC50>10 uM) IKK3, MKK4, MKK7, ERK-1, Syk, Lck, Fyn, PI3Kγ, PKA, and PKC; inhibits stress-induced NF-kappaB transactivation, chemokine-, cytokine-, and adhesion molecule expression, and T- and B-cell proliferation; inhibits cockroach allergen-induced airway inflammation and hyperreactivity and efficiently abrogates leukocyte trafficking induced by carrageenan in mice.

Delivery of Bay 65-1942 prior to ischemia significantly decreases left ventricular infarct size compared with animals receiving vehicle. Compared with sham animals, animals receiving vehicle have a significant increase in the infarct-to-area at risk (AAR) ratio (70.7±3.4 vs. 5.8±3.4%, P<0.05). This ratio is significantly reduced by treatment with Bay 65-1942 at each time point (prior to ischemia 42.7±4.1%, at reperfusion 42.7±7.5%, 2 h of reperfusion 29.4±5.2%; each group P<0.05 vs. vehicle). Animals pretreated with Bay 65-1942 (n=3) have significantly attenuated CK-MB levels compared with those animals without treatment prior to IR (14,170 ±3,219 units, P<0.05 vs. vehicle).

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. 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). 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). 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.

BAY 65-1942 | BAY-65-1942 | BAY65-1942 | BAY 651942 | BAY65-1942 free base

Immunology/Inflammation

IκB kinase (IKK)

IκB kinase (IKK)

Inflammation/Immunology

——

600734-02-9

395.4516

C22H25N3O4

>98% (HPLC)

10 mM in DMSO

OC(C=CC=C1OCC2CC2)=C1C3=NC4=C(COC(N4)=O)C([C@H]5CNCCC5)=C3

2H-Pyrido[2,3-d][1,3]oxazin-2-one, 7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-1,4-dihydro-5-(3S)-3-piperidinyl-

(-20℃)

With Ice Pack

≥ 2 years