![N-[3-[[5-Cyclopropyl-2-[[3-(4-morpholinylmethyl)phenyl]amino]-4-pyrimidinyl]amino]propyl]cyclobutanecarboxamide structure, CAS 1190378-57-4](/structures/180000/179356_1_1190378_57_4.png)
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 1190378-57-4 |
| Catalog No. | 2A-2178664 |
| Chinese Name | N-[3-[[5-环丙基-2-[[3-(4-吗啉基甲基)苯基]氨基]-4-嘧啶基]氨基]丙基]环丁烷甲酰胺 |
| Synonyms | CS-0249; 1FV; MRT68921; MRT67307 |
| Molecular Formula | C26H36N6O2 |
| Molecular Weight | 464.60 |
| Purity | ≥95 (HPLC) |
| Density | 1.3±0.1 g/cm3 |
| Appearance | solid |
| Storage Condition | -20℃ |
| Application | MRT67307 is a dual inhibitor of IKKε and TBK-1 with IC50 of 160 and 19 nM respectively. MRT67307 also inhibits ULK1 and ULK2 with IC50 of 45 and 38 nM respectively. |
| MDL Number | MFCD19443643 |
| SMILES | N5(CCOCC5)Cc1cc(ccc1)Nc2nc(c(cn2)C4CC4)NCCCNC(=O)C3CCC3 |
| InChI | 1S/C26H36N6O2/c33-25(21-5-2-6-21)28-11-3-10-27-24-23(20-8-9-20)17-29-26(31-24)30-22-7-1-4-19(16-22)18-32-12-14-34-15-13-32/h1,4,7,16-17,20-21H,2-3,5-6,8-15,18H2,(H,28,33)(H2,27,29,30,31) |
| InChI Key | UKBGBACORPRCGG-UHFFFAOYSA-N |
| NACRES Code | NA.77 |
| UNSPSC | 51111800 |
| Hazard Symbols | transportation |
| MSDS | msds/179356_1_1190378_57_4.pdf |
| Bioactivity | 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. Related Catalog Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> NF-κB >> IKK Signaling Pathways >> Autophagy >> ULK Research Areas >> Inflammation/Immunology 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 [1]. Clark K, et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104. [2]. 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. [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. Chemical & Physical Properties 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 InChIKey UKBGBACORPRCGG-UHFFFAOYSA-N SMILES O=C(NCCCNc1nc(Nc2cccc(CN3CCOCC3)c2)ncc1C1CC1)C1CCC1 Storage condition -20℃ |
| Use of | 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. Properties Name N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide Synonym More Synonyms MRT67307 Biological Activity 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. Related Catalog Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> NF-κB >> IKK Signaling Pathways >> Autophagy >> ULK Research Areas >> Inflammation/Immunology ULK1:45 nM (IC50) ULK2:38 nM (IC50) References [1]. Clark K, et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104. [2]. 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. [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. Chemical & Physical Properties Molecular Formula C26H36N6O2 Exact Mass 464.289978 PSA 98.13000 Index of Refraction 1.652 InChIKey UKBGBACORPRCGG-UHFFFAOYSA-N Storage condition -20℃ |
| Transport Info | Shipping Name: UN |
| MSDS Transport Info | Module 14. Shipping information 14.1 UN dangerous goods number European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.2 United Nations shipping name European Land Transport Dangerous Regulations: Non-dangerous goods IMDG Code: Non-dangerous goods International air transport dangerous goods regulations: non-dangerous goods 14.3 Transport hazard categories European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.4 Package group European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.5 Environmental hazards European Land Transport Danger Regulations: No International Maritime Danger Regulations International Air Transport Danger Regulations: No Marine pollutants (yes/no): No 14.6 Special reminder to users No data available See reverse side of invoice or packing slip. |
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