MRT67307 | CAS:1190378-57-4

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Name:MRT67307; 
Cat. No. :CS-0249
CAS No. :1190378-57-4
Formula:C26H36N6O2
M. Wt. : 464.60
Solubility:10 mM in DMSO

MRT67307 is a dual inhibitor of the IKKε and TBK-1, which mediates the phosphorylation of interferon regulatory factor 3 (IRF3), with IC50 values of 160 and 19 nM when assayed at 0.1 mM ATP in vitro, and also targets ULK1 and ULK2 with high potency (IC50 values of 45 and 38 nM, respectively). IC50 & Target: IC50: 160 nM (IKKε, ATP), 19 nM (TBK-1, ATP), 45 nM (ULK1), 38 nM (ULK2)In Vitro: MRT67307 actually enhances phosphorylation in IKKα−/− MEFs, the IL-1-stimulated phosphorylation of p105 at Ser933 and RelA at both Ser468 and Ser536. MRT67307 also enhances IL-1-stimulated activation of NF-κB-dependent gene transcription in wild-type MEFs. Treatment of macrophages with MRT67307 leads to an increase in the poly(I:C)- and LPS-stimulated phosphorylation of p105 and RelA and enhanced NF-κB transcriptional activity[1]. MRT67307 (10 μM) is sufficient to reduce phospho-ATG13 to control levels, and in line with the in vitro IC50 values, 10-fold less MRT68921 (1 μM) results in a similar reduction. MRT67307 and MRT68921 inhibit ULK and block autophagy in cells[2]. MRT67307 increases IL-10 production and suppresses proinflammatory cytokine production in macrophages. MRT67307 increases CREB-dependent gene transcription by promoting the dephosphorylation of CRTC3. MRT67307 does not inhibit the brain-specific kinases (BRSKs) and only inhibits the maternal embryonic leucine zipper kinase (MELK) and AMPK itself more weakly[3].

Clark K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91. Petherick KJ, et al. Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem. 2015 May 1;290(18):11376-83. Clark K, et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104.