| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
MRT-68921 HCl targets the autophagy-related kinases ULK1 (Unc-51 like autophagy activating kinase 1) and ULK2 (Unc-51 like autophagy activating kinase 2). ULK1 is a serine/threonine protein kinase that plays an essential role in the initiation of autophagy, a cellular degradation process crucial for maintaining homeostasis and responding to stress. ULK2 is a closely related homolog that shares significant functional overlap with ULK1. By acting as a dual inhibitor, MRT-68921 HCl potently suppresses the activity of both kinases, thereby effectively blocking the autophagic flux at its earliest stage.
|
|---|---|
| ln Vitro |
ULK1 is an inhibitor of serine/threonine proteins that is essential for the early phases of autophagy. Locally, MRT68921 dihydrochloride suppresses autophagy as well as uLK1 and uLK2. With an IC50 drop of more than 15 times for ULK1 (2.9 nm) and more than 30 times for uLK2 (1.1 nm), MRT68921 dihydrochloride was the most effective against ULK1 and uLK2 in the liver. ULK1 is the specific mechanism by which the molecule replicates its autophagosome structure. The increase of early autophagosome structures upon ULK1 inhibition indicates a potential role for ULK1 in the development and initiation of autophagosomes [1].
In vitro, MRT-68921 HCl demonstrates exceptionally potent inhibitory activity against its targets. It inhibits ULK1 with an IC₅₀ of 2.9 nM and ULK2 with an IC₅₀ of 1.1 nM. This makes it one of the most potent inhibitors of ULK1 and ULK2 identified to date. In cellular assays, the compound effectively blocks autophagy in various cell lines, including mouse embryonic fibroblasts. By inhibiting ULK1, MRT68921 drives the accumulation of stalled early autophagosomal structures, confirming its role in blocking the autophagic process. Furthermore, it has been shown to significantly kill tumor cells by disrupting the balance of oxidative stress signaling. |
| ln Vivo |
In vivo data for MRT-68921 HCl are less extensively documented in public literature compared to its in vitro profile. However, given its potent in vitro activity and its role as a key research tool, the compound is expected to be useful for in vivo studies investigating the role of autophagy in tumorigenesis and other diseases. Its ability to inhibit autophagy in cells provides a strong rationale for its application in animal models to evaluate the therapeutic potential of targeting ULK1/2 in cancer. Further dedicated in vivo pharmacokinetic and efficacy studies are necessary to fully characterize its profile.
|
| Enzyme Assay |
In vitro kinase assays for MRT-68921 HCl typically employ recombinant ULK1 and ULK2 enzymes. The compound is dissolved in a suitable solvent like DMSO and serially diluted in an appropriate assay buffer. The enzymatic reaction is initiated by the addition of ATP and a peptide substrate. After incubation at 30°C for a set period, the extent of phosphorylation is measured using methods such as fluorescence polarization, AlphaScreen, or radiometric techniques. IC₅₀ values are calculated by fitting dose-response data to a nonlinear regression model. For cellular target engagement, methods like immunoblotting for autophagy markers (e.g., LC3-II) are used.
|
| Cell Assay |
For cell-based assays, relevant cell lines (e.g., cancer cells or mouse embryonic fibroblasts) are cultured in appropriate media. Cells are seeded in multi-well plates and allowed to adhere before being treated with MRT-68921 HCl at various concentrations for a defined period. Following treatment, cells are lysed, and the extent of autophagy inhibition is assessed by measuring the accumulation of LC3-II or the degradation of autophagy substrates like p62 via Western blotting. Cell viability and proliferation are measured using standard assays such as MTT, CellTiter-Glo, or by counting viable cells. All experiments include appropriate vehicle controls and are performed in triplicate.
|
| Animal Protocol |
In vivo animal studies with MRT-68921 HCl are typically conducted in rodent models of cancer. The compound is formulated in a suitable vehicle, such as a mixture of DMSO, PEG300, Tween 80, and saline, and administered via routes like intraperitoneal (IP) injection. Dosing regimens, including frequency and duration, are optimized based on preliminary pharmacokinetic and tolerability studies. Endpoints for efficacy studies include the measurement of tumor volume, assessment of tumor cell proliferation and apoptosis, and analysis of autophagy markers in tumor tissue. All procedures must be conducted in accordance with institutional animal care and use committee guidelines.
|
| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of MRT-68921 HCl are not extensively reported in publicly available sources. As a small molecule, its properties such as solubility, stability, and bioavailability are critical for in vivo applications. The compound is soluble in DMSO and is typically stored as a powder at -20°C to maintain stability. For in vivo studies, it is often formulated in vehicles containing DMSO and other solubilizing agents. A comprehensive ADME (Absorption, Distribution, Metabolism, and Excretion) profile is essential for interpreting in vivo efficacy data and would be a prerequisite for any potential therapeutic development.
|
| Toxicity/Toxicokinetics |
Toxicological data for MRT-68921 HCl are primarily derived from in vitro cell viability assays and in vivo tolerability studies. As a potent inhibitor of a fundamental cellular process (autophagy), its safety profile requires careful evaluation. The compound is intended for research use only and is not for human therapeutic applications. Any potential toxicity would likely be related to its on-target effects on autophagy, which could impact normal cellular homeostasis. Comprehensive safety pharmacology and toxicology studies would be necessary to assess its risk profile for any future therapeutic development.
|
| References | |
| Additional Infomation |
MRT-68921 HCl is a research-grade chemical probe, and its primary application is in the field of autophagy and cancer research. Its potent and selective inhibition of ULK1/2 makes it an invaluable tool for dissecting the molecular mechanisms of autophagy and for validating ULK1/2 as potential therapeutic targets. The compound is not an approved drug and has not entered clinical trials. It is commercially available from various chemical suppliers exclusively for research purposes. Its discovery has significantly contributed to the understanding of autophagy's role in cancer and other diseases.
|
| Molecular Formula |
C25H36CL2N6O
|
|---|---|
| Molecular Weight |
507.498943328857
|
| Exact Mass |
506.232
|
| CAS # |
2080306-21-2
|
| Related CAS # |
MRT68921;1190379-70-4;MRT68921 hydrochloride;2070014-87-6
|
| PubChem CID |
124201611
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
34
|
| Complexity |
624
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.Cl.O=C(C1CCC1)NCCCNC1C(=CN=C(NC2C=CC3CN(C)CCC=3C=2)N=1)C1CC1
|
| InChi Key |
NLKPLTWKINJHCK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H34N6O.2ClH/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)2*1H
|
| Chemical Name |
N-(3-((5-cyclopropyl-2-((2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)amino)pyrimidin-4-yl)amino)propyl)cyclobutanecarboxamide
dihydrochloride
|
| Synonyms |
MRT68921 HCl MRT68921 hydrochloride MRT68921 MRT 68921 MRT-68921.
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~33.33 mg/mL (~65.67 mM)
DMSO : ~8.33 mg/mL (~16.41 mM) |
|---|---|
| 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 | 1.9704 mL | 9.8522 mL | 19.7044 mL | |
| 5 mM | 0.3941 mL | 1.9704 mL | 3.9409 mL | |
| 10 mM | 0.1970 mL | 0.9852 mL | 1.9704 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
