| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Leucettine L41 targets cdc2-like kinases (CLKs: CLK1, CLK2, CLK3) and dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs: DYRK1A, DYRK2). It also interacts with CK2, PIM1, and GSK-3α/β. These kinases are involved in various cellular processes including cell cycle regulation, transcription, splicing, and signal transduction.
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| ln Vitro |
Leucettine L41 shows potent inhibitory activity against its target kinases with IC50 values of 40 nM (DYRK1A), 35 nM (DYRK2), 15 nM (CLK1), and 4.5 µM (CLK3). It also inhibits GSK3α/β (0.41 µM) and Pim1 (4.1 µM). In cell-based assays, Leucettine L41 inhibits cell apoptosis and ROS production. It promotes β-cell cell cycle progression, cell proliferation, and increases insulin secretion.
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| ln Vivo |
Leucettine L41 prevents Aβ25-35-induced memory impairments and neurotoxicity in the mouse hippocampus. This suggests neuroprotective activity in models of Alzheimer's disease. The compound induces mTOR-dependent autophagy. It also promotes β-cell proliferation and insulin secretion, indicating potential applications in diabetes research.
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| Enzyme Assay |
Kinase inhibition is assessed using in vitro kinase assays with purified recombinant kinases (DYRK1A, DYRK2, CLK1, CLK3, GSK3α/β, Pim1) and appropriate peptide substrates. Assays measure the incorporation of [γ-³²P]-ATP into substrates or use luminescent ADP detection. Leucettine L41 is incubated at various concentrations, and IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell-based assays are performed in various cell lines including neuronal cells and β-cell lines. Apoptosis is assessed using Annexin V/PI staining or caspase activity assays. ROS production is measured using fluorescent probes such as DCFH-DA. Cell cycle progression and proliferation are evaluated by flow cytometry and BrdU incorporation assays. Insulin secretion is measured by ELISA or radioimmunoassay in β-cell lines or isolated islets.
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| Animal Protocol |
Leucettine L41 is administered to mice to evaluate its effects on memory and neurotoxicity. In the Aβ25-35-induced memory impairment model, Leucettine L41 is typically administered intraperitoneally or orally prior to or following Aβ injection. Memory is assessed using behavioral tests such as the Morris water maze or novel object recognition test. Hippocampal tissue is collected for analysis of neurotoxicity markers and autophagy markers.
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| ADME/Pharmacokinetics |
Leucettine L41 has a molecular weight of 307.3 and molecular formula C17H13N3O3. Purity is typically >98% (NMR). The compound appears as a beige solid. It is soluble in DMSO or ethanol. Storage is recommended at -20°C. Leucettine L41 is a dual inhibitor of CLKs and DYRKs and is used as a research tool in neuroscience and oncology.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of Leucettine L41 have not been extensively reported. The compound has shown neuroprotective activity and prevents Aβ-induced neurotoxicity in the mouse hippocampus, suggesting a favorable safety profile in the brain. It induces mTOR-dependent autophagy, which could have both beneficial and adverse effects depending on the context. Further toxicological studies are needed.
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| References |
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| Additional Infomation |
Leucettine L41 belongs to the benzodioxane class of compounds, with the structure 1,3-benzodioxane, substituted at the 5-position by a (2-aniline-5-oxo-1,5-dihydro-4H-imidazol-4-yl)methyl group. It is an inhibitor of DYRK1A, DYRK2, CLK1, and CLK3 (IC50 values of 0.04, 0.035, 0.015, and 4.5 μM, respectively). It possesses multiple functions, including autophagy induction, EC 2.7.12.1 (bispecific kinase) inhibition, nootropic effect, neuroprotective effect, and EC 2.7.11.22 (cyclin-dependent kinase) inhibition. It belongs to the benzodioxane, substituted aniline, and imidazolide classes of compounds.
Leucettine L41 (CAS#: 1112978-84-3) is a novel potent dual inhibitor of CLKs and DYRKs with IC50 values in the nanomolar to micromolar range. It induces mTOR-dependent autophagy, prevents Aβ25-35-induced memory impairments and neurotoxicity in the mouse hippocampus, and promotes β-cell proliferation and insulin secretion. The compound is a valuable research tool for studying kinase biology in neurodegeneration, diabetes, and cancer. |
| Molecular Formula |
C17H13N3O3
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|---|---|
| Molecular Weight |
307.3034
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| Exact Mass |
307.095
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| CAS # |
1112978-84-3
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| Related CAS # |
1112978-84-3
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| PubChem CID |
135398522
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| Appearance |
Light yellow to yellow solid
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.698
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| LogP |
3.49
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
525
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1COC2C=CC(C=C3C(NC(=N3)NC3C=CC=CC=3)=O)=CC1=2
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| InChi Key |
PGPHHJBZEGSUNE-JYRVWZFOSA-N
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| InChi Code |
InChI=1S/C17H13N3O3/c21-16-13(8-11-6-7-14-15(9-11)23-10-22-14)19-17(20-16)18-12-4-2-1-3-5-12/h1-9H,10H2,(H2,18,19,20,21)/b13-8-
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| Chemical Name |
(4Z)-2-anilino-4-(1,3-benzodioxol-5-ylmethylidene)-1H-imidazol-5-one
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| Synonyms |
Leucettine L41
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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) |
DMSO: ~125 mg/mL (~406.8 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.14 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication and warming and heat to 80°C.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2541 mL | 16.2707 mL | 32.5415 mL | |
| 5 mM | 0.6508 mL | 3.2541 mL | 6.5083 mL | |
| 10 mM | 0.3254 mL | 1.6271 mL | 3.2541 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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