1. NF-κB
    Autophagy
  2. IKK
    Autophagy

MRT67307 

Cat. No.: HY-13018 Purity: 99.02%
Data Sheet SDS Handling Instructions

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).

For research use only. We do not sell to patients.
MRT67307 Chemical Structure

MRT67307 Chemical Structure

CAS No. : 1190378-57-4

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $88 In-stock
5 mg $80 In-stock
10 mg $130 In-stock
50 mg $550 In-stock
100 mg $710 In-stock
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Customer Review

    MRT67307 purchased from MCE. Usage Cited in: Nat Commun. 2015 Jan 21;6:6074.

    MRT67307 efficiently inhibits the AKT degradation. IB analysis using WT CD4+ T cells, pretreated for 1 h with a TBK1 inhibitor, MRT67307, of solvent control DMSO and subsequently stimulated for the indicated times with anti-CD3 plus anti-CD28 in the presence of a protein synthesis inhibitor, Cycloheximide.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    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].

    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 2.1524 mL 10.7619 mL 21.5239 mL
    5 mM 0.4305 mL 2.1524 mL 4.3048 mL
    10 mM 0.2152 mL 1.0762 mL 2.1524 mL
    Kinase Assay
    [1]

    Substrates and kinases are diluted in 50 mM Tris/HCl (pH 7.5), 0.1% 2-mercaptoethanol, 0.1 mM EGTA and 10 mM magnesium acetate. Reactions are initiated with [γ-32P]ATP (2500 c.p.m./pmol) to a final concentration of 0.1 mM and terminated after 15 min at 30°C by the addition of SDS and EDTA (pH 7.0) to final concentrations of 1.0% (w/v) and 20 mM respectively. After heating for 5 min at 100°C and separation by SDS/PAGE, the phosphorylated proteins are detected by autoradiography. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [3]

    Cells are rinsed in ice-cold PBS and extracted in lysis buffer (50 mM Tris·HCl at pH 7.4, 1 mM EDTA, 1 mM EGTA, 50 mM NaF, 5 mM sodium pyrophosphate, 10 mM sodium β-glycerol 1-phosphate, 1 mM DTT, 1 mM sodium orthovanadate, 0.27mol/Lsucrose, 1% (vol/vol) Triton X-100, 1 μg/mL aprotinin, 1 μg/ mL leupeptin, and 1 mM phenylmethylsulphonyl fluoride). Cell extracts are clarified by centrifugation at 14,000 × g for 10 min at 4°C, and protein concentrations are determined by using the Bradford assay. FLAG-CRTC3 is purified on anti-FLAG M2 agarose, whereas endogenous CRTC3 is immunoprecipitated from cell extracts by using anti-CRTC3 raised against the peptide CWKEEKHPGFR (S277D bleed 2) and coupled to Protein GSepharose. To detect proteins in cell lysates, 20 μg of protein extract is separated by SDS/PAGE. After transfer to PVDF membranes, proteins are detected by immunoblotting and visualized by treating the blots with ECL followed by autoradiography. The following antibodies are used for immunoblotting: pSer133 CREB, pSer171 CRTC2, total CRTC2, GAPDH, total STAT3, pTyr705 STAT3, FLAG (M2 clone), CRTC3, HA (3F10), and 14-3-3; and antibodies against pSer329 (S256D bleed 2) and pSer370 (S253D bleed 2) of CRTC3 are raised against the phosphopeptides GLQSSRpSNPSIQ and RLFSLpSNPSLST. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    464.6

    Formula

    C₂₆H₃₆N₆O₂

    CAS No.

    1190378-57-4

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Product Name:
    MRT67307
    Cat. No.:
    HY-13018
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