MRT67307 is a kinase inhibitor that has been shown to inhibit TBK1, MARK1-4, IKKε, and NUAK1 (IC₅₀values are 19, 27-52, 160, and 230 nM, respectively), the salt-inducible kinases (SIKs; IC₅₀s = 250, 67, and 430 nM for SIK1, SIK2, and SIK3, respectively) and ULK1 and ULK2 (IC₅₀s = 45 and 38 nM, respectively).^1,2,3,4MRT67307 prevents the phosphorylation of IRF3 and the production of IFN-β and increases toll-like receptor-induced IL-10 and IL-1ra secretion in macrophages.^1,3Through its effects on ULK1 and ULK2, MRT67307 blocks autophagy.⁴

1.Clark, K., Peggie, M., Plater, L., et al.Novel cross-talk within the IKK family controls innate immunityBiochem. J.434(1)93-104(2011) 2.Clark, K., Takeuchi, O., Akira, S., et al.The TRAF-associated protein TANK facilitates cross-talk within the IkappaB kinase family during Toll-like receptor signalingProc. Natl. Acad. Sci. USA108(41)17093-17098(2011) 3.Clark, K., MacKenzie, K.F., Petkevicius, K., et al.Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophagesProc. Natl. Acad. Sci. USA109(42)16986-16991(2012) 4.Petherick, K.J., Conway, O.J.L., Mpamhanga, C., et al.Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagyJ. Biol. Chem.290(18)11376-11383(2015)