| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
MRT68921 hydrochloride targets ULK1 (unc-51-like autophagy activating kinase 1) and ULK2, which are serine/threonine protein kinases that play essential roles in the initiation of autophagy. ULK1 and ULK2 are key components of the autophagy initiation complex, and their activation is required for the formation of autophagosomes. By potently inhibiting ULK1 and ULK2 with IC₅₀ values of 2.9 nM and 1.1 nM, respectively, MRT68921 hydrochloride effectively blocks autophagy in cells, leading to disruption of cellular homeostasis and induction of cell death.
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| ln Vitro |
The serine/threonine protein kinase ULK1 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. The buildup of early autophagosome structures that have stalled due to ULK1 inhibition suggests that ULK1 is involved in the maturation and initiation of autophagosomes [1].
In vitro, MRT68921 hydrochloride potently inhibits ULK1 and ULK2 with IC₅₀ values of 2.9 nM and 1.1 nM, respectively. The compound prevents autophagy in cells and inhibits ULK1 and ULK2 in vitro. MRT68921 hydrochloride is the most effective inhibitor of ULK1 and ULK2, reducing the IC₅₀ for both ULK1 and ULK2 by more than 15 and 30 times, respectively. The compound's ability to inhibit autophagy is mediated through ULK1, and it can kill tumor cells by breaking the balance of oxidative stress signals. |
| ln Vivo |
In vivo activity data for MRT68921 hydrochloride are limited. Based on its potent in vitro inhibition of ULK1 and ULK2 and its ability to block autophagy and kill tumor cells, the compound is expected to demonstrate antitumor efficacy in animal models of cancer. Typical in vivo studies for ULK inhibitors involve administration to tumor-bearing mouse models, with assessment of tumor growth inhibition, autophagy markers, and survival.
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| Enzyme Assay |
For non-cellular in vitro enzyme assays, MRT68921 hydrochloride is evaluated for its inhibitory activity against purified ULK1 and ULK2 kinases. The compound is incubated with ULK1 or ULK2, ATP, and a substrate peptide in kinase buffer. The phosphorylation of the substrate is measured using radioactive labeling, fluorescence, or antibody-based detection methods. The IC₅₀ values are determined from dose-response curves, with values of 2.9 nM for ULK1 and 1.1 nM for ULK2.
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| Cell Assay |
For in vitro cellular assays, MRT68921 hydrochloride is tested in various cell lines to assess its effects on autophagy and cell viability. Cells are treated with serial dilutions of the compound, and autophagy is assessed by measuring LC3-II levels (a marker of autophagosome formation) and p62 levels (a marker of autophagic flux) by Western blot. Cell viability is measured using standard assays. The compound's ability to kill tumor cells by breaking the balance of oxidative stress signals may be assessed by measuring reactive oxygen species levels.
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| Animal Protocol |
For in vivo animal studies, MRT68921 hydrochloride would typically be evaluated in xenograft mouse models of cancer. Mice bearing established tumors are treated with the compound at various doses via intraperitoneal or oral administration. Tumor volumes are measured regularly, and autophagy markers (LC3-II, p62) are assessed in tumor tissues at study endpoint. Body weight and general health are monitored to evaluate tolerability.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for MRT68921 hydrochloride are limited. As a small-molecule kinase inhibitor with a molecular weight of 471.04, it is expected to have moderate oral bioavailability and tissue distribution. The compound is soluble in DMSO and can be formulated for in vivo administration. Further pharmacokinetic studies would be needed to determine its absorption, distribution, metabolism, and excretion profile. The compound is for research use only and not for human use.
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| Toxicity/Toxicokinetics |
Toxicological data for MRT68921 hydrochloride are limited. As a potent ULK1/ULK2 inhibitor that blocks autophagy, the compound may have on-target toxicities related to the essential role of autophagy in maintaining cellular homeostasis in various tissues. Comprehensive toxicology studies including acute and repeat-dose toxicity, genotoxicity, and organ-specific toxicity assessments would be required for therapeutic development. The compound is for research use only and not for human use.
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| References | |
| Additional Infomation |
MRT68921 hydrochloride is a potent inhibitor of both ULK1 and ULK2 with IC₅₀ values of 2.9 nM and 1.1 nM, respectively. It is the most effective inhibitor of ULK1 and ULK2 identified to date. MRT68921 hydrochloride can block cellular autophagy and kill tumor cells by breaking the balance of oxidative stress signals. The compound's inhibition of autophagy is mediated through ULK1. MRT68921 hydrochloride has a molecular weight of 471.04 and molecular formula C₂₅H₃₅ClN₆O.
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| Molecular Formula |
C25H35CLN6O
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|---|---|
| Molecular Weight |
471.04
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| Exact Mass |
470.256
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| CAS # |
2070014-87-6
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| Related CAS # |
MRT68921;1190379-70-4;MRT68921 dihydrochloride;2080306-21-2
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| PubChem CID |
121230974
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
33
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| Complexity |
624
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C(C1CCC1)NCCCNC1C(=CN=C(NC2C=CC3CN(C)CCC=3C=2)N=1)C1CC1
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| InChi Key |
SCEOGAWLKSVXHH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H34N6O.ClH/c1-31-13-10-19-14-21(9-8-20(19)16-31)29-25-28-15-22(17-6-7-17)23(30-25)26-11-3-12-27-24(32)18-4-2-5-18;/h8-9,14-15,17-18H,2-7,10-13,16H2,1H3,(H,27,32)(H2,26,28,29,30);1H
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| Chemical Name |
N-[3-[[5-cyclopropyl-2-[(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)amino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide;hydrochloride
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| 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)
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| 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
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1230 mL | 10.6148 mL | 21.2296 mL | |
| 5 mM | 0.4246 mL | 2.1230 mL | 4.2459 mL | |
| 10 mM | 0.2123 mL | 1.0615 mL | 2.1230 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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