N-(4-Pyrrolidin-1-yl-piperidin-1-yl)-[4-(4-benzo[b]thiophen-2-yl-pyrimidin-2-ylamino)phenyl]carboxamidehydrochloride

Uses

IKK-16 Hydrochloride is a potential novel IκB kinase 2 (IKK2) inhibitor used in the treatment of various immune/inflammatory disorders.

Biological Activity

ikk-16 is an iκb kinases (ikks) inhibitor.the iκb kinase (ikk), part of a high molecular weight protein complex consisting of three subunits, ikk1, ikk2, and ikkc, emerged as a prime target for the development of novel anti-rheumatic and anti-inflammatory drugs.

in vitro

in screening study, it was found that compounds with an additional basic amino group were more active than the neutral inhibitors. the tertiary amines, such as ikk-16, was active in the low-nanomolar range. ikk-16 could inhibit tnfa-induced adhesion molecule expression in a potency range similar to the ijba degradation. although ikk-16 showed activity in the ifnc-induced expression of b2 microglobulin, its potency was weaker. these data demonstrated that ikk-16 had an effect on downstream gene expression, however, on the cellular level the selectivity was modest [1].

in vivo

animal study found that the treatment with ikk 16 to mice could attenuate the impairment in systolic contractility, renal dysfunction, hepatocellular injury and lung inflammation in lps/pepg-induced mod and in polymicrobial sepsis. ikk-16 treatment could also significantly attenuated the increase in inducible nitric oxide synthase (inos) expression and increase the phosphorylation of akt and endothelial nitric oxide synthase [2].

IC 50

200, 40, and 70 nm for ikkα, ikkβ, and ikk complex, respectively.

storage

Desiccate at -20°C

References

[1] waelchli, r. ,bollbuck, b.,bruns, c., et al. design and preparation of 2-benzamido-pyrimidines as inhibitors of ikk. bioorganic & medicinal chemistry letters 16(1), 108-112 (2006).
[2] coldewey, s. m.,rogazzo, m.,collino, m., et al. inhibition of i k b kinase reduces the multiple organ dysfunction caused by sepsis in the mouse. dis.model mech. 6, 1031-1042 (2013).