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| 10mg |
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| 25mg |
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MRT-68921 (MRT68921; MRT 68921) is a novel, potent and dual inhibitor of the autophagy kinase ULK1 and ULK2 with IC50s of 2.9 and 1.1 nM, respectively. Autophagy is found to be a critical cell-degradative and protective process recycling damaged and long-lived cellular components. ULK1 is a serine/threonine protein kinase that is important for the initial stages of autophagy. MRT68921 was identified to be relatively specific, but still could inhibit a number of kinases by over 80%. Most importantly, TBK1/IKK as well as the AMPK-related kinases were still found to be targeted. Moreover, by using LKB1 knock-out MEFs, it was found that LC3 flux was comparable with matched, wild-type MEFs and could be inhibited to the same extent in the treatment with MRT68921. Thus, these kinases are suggested to be not the target of MRT68921 in blocking autophagy. In addition, MRT68921 was found to be able to block the WT-restored ATG13 phosphorylation and autophagy, which was similar to cells expressing endogenous ULK1. In contrast, in cells expressing a similar level of M92T ULK1, MRT68921 could not reduce either ATG13 phosphorylation or LC3 flux, which indicated that MRT68921 was truly able to block autophagy via ULK1 kinase inhibition.
| ln Vitro |
ULK1 is a serine/threonine protein kinase that is necessary for autophagy's early phases. MRT68921 prevents autophagy in cells and inhibits ULK1 and ULK2 in vitro. The most effective inhibitor of ULK1 and ULK2, MRT68921, reduces the IC50 for both ULK1 (2.9 nm) and ULK2 (1.1 nm) by more than 15 and 30 times, respectively. This compound's particular capacity to suppress autophagy is made possible by ULK1. ULK1 may be involved in the maturation and initiation of autophagosomes, as evidenced by the buildup of stalled early autophagosome structures upon ULK1 inhibition [1].
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| References |
[1]. 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
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| Molecular Formula |
C27H36N4O
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|---|---|
| Molecular Weight |
432.6009
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| CAS # |
1190379-70-4
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| Related CAS # |
MRT68921 dihydrochloride;2080306-21-2;MRT68921 hydrochloride;2070014-87-6
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| SMILES |
O=C(C1CCC1)NCCCNC2=CC(NC3=CC4=C(CN(C)CC4)C=C3)=CC=C2C5CC5
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| InChi Key |
JGKCPXMSBDYENM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H36N4O/c1-31-15-12-21-16-23(9-8-22(21)18-31)30-24-10-11-25(19-6-7-19)26(17-24)28-13-3-14-29-27(32)20-4-2-5-20/h8-11,16-17,19-20,28,30H,2-7,12-15,18H2,1H3,(H,29,32)
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| Chemical Name |
Cyclobutanecarboxylic acid {3-[2-cyclopropyl-5-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-6-ylamino)-phenylamino]-propyl}-amide
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| Synonyms |
MRT68921 MRT-68921 MRT 68921
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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)
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| 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3116 mL | 11.5580 mL | 23.1160 mL | |
| 5 mM | 0.4623 mL | 2.3116 mL | 4.6232 mL | |
| 10 mM | 0.2312 mL | 1.1558 mL | 2.3116 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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