1190378-57-4
1190378-57-4 structure
- Name: MRT67307
- Chemical Name: N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide
- CAS Number: 1190378-57-4
- Molecular Formula: C26H36N6O2
- Molecular Weight: 464.603
- Catalog: Signaling Pathways Autophagy Autophagy
- Create Date: 2019-01-02 23:44:06
- Modify Date: 2024-01-02 10:07:35
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MRT67307 is a dual inhibitor of the IKKε and TBK-1 with IC50s of 160 and 19 nM, respectively. MRT67307 also inhibits ULK1 and ULK2 with IC50s of 45 and 38 nM, respectively.
| Name | N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide |
|---|---|
| Synonyms |
CS-0249
1FV N-{3-[(5-Cyclopropyl-2-{[3-(Morpholin-4-Ylmethyl)phenyl]amino}pyrimidin-4-Yl)amino]propyl}cyclobutanecarboxamide Cyclobutanecarboxamide, N-[3-[[5-cyclopropyl-2-[[3-(4-morpholinylmethyl)phenyl]amino]-4-pyrimidinyl]amino]propyl]- N-{3-[(5-Cyclopropyl-2-{[3-(4-morpholinylmethyl)phenyl]amino}-4-pyrimidinyl)amino]propyl}cyclobutanecarboxamide cyclobutanecarboxylic acid {3-[5-cyclopropyl-2-(3-morpholin-4-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-amide MRT68921 MRT67307 |
| Description | MRT67307 is a dual inhibitor of the IKKε and TBK-1 with IC50s of 160 and 19 nM, respectively. MRT67307 also inhibits ULK1 and ULK2 with IC50s of 45 and 38 nM, respectively. |
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| Related Catalog | |
| Target |
TBK1:19 nM (IC50, at 0.1 mM ATP) IKKε:160 nM (IC50, at 0.1 mM ATP) ULK1:45 nM (IC50) ULK2:38 nM (IC50) Autophagy |
| 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]. |
| Kinase Assay | 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. |
| Cell Assay | 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. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Molecular Formula | C26H36N6O2 |
| Molecular Weight | 464.603 |
| Exact Mass | 464.289978 |
| PSA | 98.13000 |
| LogP | 1.30 |
| Index of Refraction | 1.652 |
| Storage condition | -20℃ |