MRT67307 (MRT-67307; MRT 67307) is a novel and potent inhibitor for multiple kinases such as TBK1, IKKε , MARK1-4 and NUAK1 with potential antineoplastic activity. It inhibits TBK1, IKKε , MARK1-4 and NUAK1 with IC50s of 19, 160, 27-52 and 230nM, respectively.
Physicochemical Properties
| Molecular Formula | C26H36N6O2 | |
| Molecular Weight | 464.6 (free-base) | |
| Exact Mass | 464.289 | |
| CAS # | 1190378-57-4 | |
| Related CAS # | MRT67307 hydrochloride;2095432-39-4;MRT67307 dihydrochloride;1781882-89-0 | |
| PubChem CID | 44464263 | |
| Appearance | Light yellow to yellow solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Index of Refraction | 1.652 | |
| LogP | 1.3 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 7 | |
| Rotatable Bond Count | 11 | |
| Heavy Atom Count | 34 | |
| Complexity | 637 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | UKBGBACORPRCGG-UHFFFAOYSA-N | |
| InChi Code | 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) | |
| Chemical Name | N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | MRT67307 inhibits TBK1 and IKKε in vitro at 0.1 mM ATP with IC50 values of 160 and 19 nM, respectively, but not IKKα or IKKβ, not even at 10 μM [1]. MRT67307 (2 μM) inhibits bone marrow-derived macrophages (BMDM) from phosphorylating IRF3. Poly (I:C) does not prevent JNK or p38 MAPK from being activated by MRT67307 (2 μM)[1]. MRT67307 (1 nM–10 μM) inhibits macrophages' ability to produce IFNβ [1]. It just takes 10 μM of MRT67307 to bring phosphorylated ATG13 down to control levels [2]. In mouse embryonic fibroblasts (MEFs), autophagy is inhibited by MRT67307 (10 μM) [2]. In 293T cells, TBK1/IKKε-induced CYLD phosphorylation is eliminated by MRT67307 (5 μM; 4 h) [3]. | ||
| ln Vivo |
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| Cell Assay |
Western Blot Analysis[3] Cell Types: 293T cells Tested Concentrations: 5 µM Incubation Duration: 4 hrs (hours) Experimental Results: Abrogated TBK1/IKKε-induced CYLD phosphorylation. |
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| Animal Protocol |
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| References |
[1]. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104. [2]. Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem. 2015 May 1;290(18):11376-83. [3]. Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. 26.37Cancer Discov. 2014 Apr;4(4):452-65. |
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| Additional Infomation | N-[3-[[5-cyclopropyl-2-[3-(4-morpholinylmethyl)anilino]-4-pyrimidinyl]amino]propyl]cyclobutanecarboxamide is an aromatic amine. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |