Table 5.
Publications in which MRT67307 was used.
| References | Intended target | Other targets | IC50 [nM] | Effect of inhibitor treatment | Confirmation of inhibitor effects | Concentration |
|---|---|---|---|---|---|---|
| Clark et al., 2011a | TBK1/IKKε | 19/160 | Inhibition of PolyI:C induced IRF3 phosphorylation, but not JNK and p38 phosphorylation and reduced LPS-induced IFNβ production in macrophages; Enhanced NF-κB activation in response to IL-1 or TNF and PolyI:C or LPS in MEF cells and macrophages, respectively | 2μM | ||
| Gleason et al., 2011 | TBK1/IKKε | Reduced OPTN phosphorylation in LPS-treated BMDMs in combination with TAK1 inhibitor 5Z-7-oxozeanol. | ||||
| Smith et al., 2011 | TBK1/IKKε | Inhibition of LPS-induced Pellino-1 induction and IRF3 phosphorylation in BMDMs; Reduced IKKε and TBK1 dependent Pellino 1 phosphorylation in vitro; Reduced LPS- or PolyI:C-induced Pellino 1 activation in macrophages | 2μM | |||
| Clark et al., 2011b | TBK1/IKKε | Increased TBK1 and IKKε activationin Pam3CSK4 stimulated BMDMs | IKKε and TBK1 knockout MEF cells | 2μM | ||
| Dzamko et al., 2012 | TBK1/IKKε | Inhibition of phosphorylation of LRRK2 in Pam3CSK4 stimulated RAW 264.7 cells | 2μM | |||
| Liu et al., 2012 | TBK1 | Abrogation of thapsigargin-dependent IRF3 phosphorylation in MEF cells | 2μM | |||
| Bruni et al., 2013 | TBK1/IKKε | Reduced ERK phosphorylation in response to PolyI:C in BMDMs | IKKε and TBK1 knockout BMDMs | 2μM | ||
| Jiang et al., 2015 | TBK1/IKKε | Decreased IFN-λ1 mRNA expression in short dsRNA-stimulated human monocyte-derived DCs | 0.1–10μM | |||
| Zhu et al., 2014 | TBK1/IKKε | Impaired CYLD (Ser418) phosphorylation upon co-expression with IKKε/TBK1 in HEK cells; decreased LPS-induced expression of IFNβ1, CCL5 and IL-6 in RAW 264.7 cells; impaired viability of KRAS-dependent A549 and HCC44 cells | genetic evidence (Tbk1−/− MEFs), independent inhibitor (CYT387) | 0.1–10μM | ||
| Lopez-Pelaez et al., 2014 | TBK1/IKKε | Inhibition of in vitro phosphorylation of IRF5 by TBK1; no effect on nuclear translocation of IRF5 upon CL097 (TLR7/8) in RAW 264.7 cells | 2μM | |||
| Awuh et al., 2015 | TBK1 | Decreased NF-κB and IRF-1 nuclear translocation in response to M. avium infection in monocyte derived macrophages; Increased M. avium growth | independent inhibitor (BX795) | 5μM | ||
| Pillai et al., 2015 | TBK1 | Inhibition of mitotic progression and formation of multinucleate cells in H460 and HeLa cells | independent inhibitor (BX795) (knockdown in additional experiments) | 2μM | ||
| Yu et al., 2015 | TBK1 | Inhibition of AKT degradation in anti-CD3/CD28 stimulated CD4+ T cells in the presence of cycloheximide | 2μM | |||
| Bruni et al., 2015 | TBK1/IKKε | Increased viral RNA production in pDCs infected with yellow fever life vaccine and reduced type I IFN production | 1μM | |||
| Saric et al., 2016 | TBK1 | No effect on LPS-induced lysosome tubulation in RAW 264.7 macrophages; inhibition of LPS-induced IRF3 phosphorylation | 2μM | |||
| Heo et al., 2015 | TBK1 | Inhibition of recruitment of OPTN, NDP52 and SQSTM1 to depolarized mitochondria in Antimycin A and Oligomycin A treated HeLa cells | TBK1−/− cells | 2μM | ||
| Swamy et al., 2015 | TBK1/IKKε | Reduced Ifnα and Ifnl mRNA induction, but no effect on Ifnγ upregulation in CD3-stimulated intestinal intraepithelial lymphocytes | 1μM | |||
| Schweitzer et al., 2016 | TBK1/IKKε | Marginal decrease in phosphorylation of IκBα and RelA (Ser468) in the cytosol and RelA nuclear translocation in TNF-stimulated HeLa cells | 10μM | |||
| Achard et al., 2017 | TBK1/IKKε | Impaired IFNα production and TRAIL expression in response to measles virus infection or R837 (TLR7 agonist) stimulation in plasmacytoid DCs; Reduced TRAIL expression in response to type I IFN | 8μM | |||
| Clark et al., 2012 | SIK1 | 250 | Increased TLR-induced expression of anti-inflammatory cytokines (IL-10 and IL-1ra) in macrophages | Structurally different inhibitors (MRT199665, HG-9-91-01, KIN112), genetic evidence (LKB1−/− macrophages) | 2μM | |
| SIK2 | 67 | |||||
| SIK3 | 430 | |||||
| MARK1-4 | 27-52 | |||||
| NUAK1 | 230 | |||||
| MacKenzie et al., 2013 | SIK | Increased LPS-induced IL-10 mRNA in BMDMs | Independent inhibitor (KIN112) | 2μM | ||
| Petherick et al., 2015 | ULK1 | 45 | Reduced amino acid starvation-induced ATG13 phosphorylation and autophagy in MEF cells | Structurally different inhibitor (MRT68921) | 10μM | |
| ULK2 | 38 | |||||
| Lazarus and Shokat, 2015 | ULK1/2 | Inhibition of autophagy (LC3 II accumulation) in HeLa cells | Independent inhibitor (BX795) | 4μM | ||
| Draz et al., 2017 | ULK1/2 | Sensitization of LNCaP and C42B cells to cell death in the presence of subtoxic concentrations of 3,3′-diindolylmethane | 10μM |