Biological Activity
MRT67307 is a potent and dual IKKε and TBK1 inhibitor with IC50 of 160 and 19 nM, respectively. MRT67307 potently inhibits ULK1 and ULK2 and blocks autophagy.
In macrophages, MRT67307 prevents the phosphorylation of IRF3 and the production of IFNβ. In wild-type MEFs, MRT67307 enhances the IL-1-stimulated phosphorylation of p105 at Ser933 and RelA at both Ser468 and Ser536, and also enhances IL-1-stimulated activation of NF-κB-dependent gene transcription. [1] MRT67307 increases IL-10 production and suppresses proinflammatory cytokine production via a cAMP response element-Binding protein (CREB)-regulated transcriptional coactivator (CRTC) 3 Dependent Mechanism. [2] In addition, MRT67307 inhibit ULK and block autophagy in MEF cells. [3]
References
[1] Clark K, et al. Biochem J. 2011, 434(1), 93-104.
[2] Clark K, et al. Proc Natl Acad Sci U S A. 2012, 109(42), 16986-16991.
[3] Petherick KJ, et al. J Biol Chem. 2015, 290(18), 11376-11383.
