| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
IKKε (I-kappa-B kinase epsilon, IKBKE), TBK-1 (TANK binding kinase 1), ULK1, ULK2, MARK1-4, NUAK1
|
|---|---|
| ln Vitro |
MRT67307 did not inhibit IKKα or IKKβ even at 10 μM, however it did inhibit IKKϵ and TBK1 with IC50 values of 160 and 19 nM when 0.1 mM ATP was detected in vitro [1]. In bone marrow-derived macrophages (BMDM), MRT67307 (2 μM) inhibits the phosphorylation of IRF3. Poly(I:C) activation of JNK and p38 MAPK is not inhibited by MRT67307 (2 μM) [1]. IFNβ production in macrophages is inhibited by MRT67307 (1 nM–10 μM) [1]. To get phospho-ATG13 down to acceptable levels, MRT67307 (10 μM) is adequate [2]. In mouse embryonic fibroblasts (MEFs), MRT67307 (10 μM) inhibits autophagy [2]. In 293T cells, MRT67307 (5 µM; 4 hours) completely eliminates TBK1/IKKε-induced CYLD phosphorylation [3].
MRT67307 inhibits TBK1 with IC50 of 19 nM and IKKε with IC50 of 160 nM when assayed at 0.1 mM ATP in vitro. It also targets ULK1 and ULK2 with IC50 values of 45 and 38 nM, respectively, and inhibits MARK1-4 (IC50 27-52 nM) and NUAK1 (IC50 230 nM). MRT67307 does not inhibit IKKα or IKKβ even at 10 μM. |
| ln Vivo |
In cellular models, MRT67307 blocks TBK1-mediated IRF3 phosphorylation and interferon production in response to viral infection. In vivo, MRT67307 has been used to study autophagy regulation and innate immune responses in mouse models, demonstrating dose-dependent inhibition of TBK1-dependent signaling pathways.
|
| Enzyme Assay |
Recombinant TBK1 and IKKε kinases were incubated with serial dilutions of MRT67307 in kinase reaction buffer containing 0.1 mM ATP and synthetic peptide substrate. Phosphorylated substrate was detected and quantified to determine IC50 values. Selectivity was assessed against IKKα, IKKβ, and other related kinases to confirm target specificity.
|
| Cell Assay |
Western Blot Analysis[3]
Cell Types: 293T Cell Tested Concentrations: 5 µM Incubation Duration: 4 hrs (hours) Experimental Results: Elimination of TBK1/IKKε-induced CYLD phosphorylation. Cells (e.g., macrophages, dendritic cells, or reporter cell lines) were cultured in appropriate media and treated with MRT67307 at various concentrations prior to stimulation with TLR ligands or viral RNA analogs. IRF3 phosphorylation and IFN-β production were measured by Western blot and ELISA. Autophagy flux was assessed by LC3 lipidation analysis and fluorescence microscopy. |
| Animal Protocol |
Mice were treated with MRT67307 by oral gavage or intraperitoneal injection at doses of 10-50 mg/kg prior to or following immune challenge with poly(I:C) or viral infection. Serum cytokine levels (IFN-β, IL-6, TNF-α) were measured by ELISA. Tissue samples were collected for Western blot analysis of TBK1 and IRF3 phosphorylation. Autophagy markers in liver and spleen were assessed by immunohistochemistry.
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| References |
|
| Additional Infomation |
N-[3-[[5-cyclopropyl-2-[3-(4-morpholinylmethyl)anilino]-4-pyrimidinyl]amino]propyl]cyclobutanecarboxamide is an aromatic amine.
|
| Molecular Formula |
C26H37CLN6O2
|
|---|---|
| Molecular Weight |
501.06
|
| Exact Mass |
464.289
|
| CAS # |
2095432-39-4
|
| Related CAS # |
MRT67307;1190378-57-4;MRT67307 dihydrochloride;1781882-89-0
|
| PubChem CID |
44464263
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4
|
| 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
|
| SMILES |
C1CC(C1)C(=O)NCCCNC2=NC(=NC=C2C3CC3)NC4=CC=CC(=C4)CN5CCOCC5.Cl
|
| 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
|
| Synonyms |
MRT67307 HCl MRT-67307 HCl
|
| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9958 mL | 9.9788 mL | 19.9577 mL | |
| 5 mM | 0.3992 mL | 1.9958 mL | 3.9915 mL | |
| 10 mM | 0.1996 mL | 0.9979 mL | 1.9958 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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