| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
DLK-IN-1 targets dual leucine zipper kinase (DLK, MAP3K12), a member of the mixed-lineage kinase family that is involved in neuronal stress responses and neurodegenerative disease pathways. DLK is a key regulator of axonal degeneration and neuronal cell death. The compound shows selectivity for DLK with a Ki of 3 nM. It also inhibits Flt3 and maintains good CNS penetration.
|
|---|---|
| ln Vitro |
DLK-IN-1 demonstrates potent in vitro inhibition of DLK with a Ki of 3 nM. The compound shows selectivity for DLK and inhibits Flt3. DLK-IN-1 is orally active and blood-brain barrier penetrable. It has good activity in cellular models relevant to neurodegenerative diseases. The compound maintains good CNS penetration, making it suitable for neurological disease research.
|
| ln Vivo |
In vivo, DLK-IN-1 demonstrates good activity in animal models of Alzheimer's disease. The compound is well tolerated after intracerebral overdose. DLK-IN-1 is orally active and maintains good penetration into the central nervous system. The compound's activity in Alzheimer's disease models supports its potential as a therapeutic agent for neurodegenerative diseases. DLK-IN-1 shows favorable CNS distribution.
|
| Enzyme Assay |
In vitro enzyme assays for DLK-IN-1 typically employ recombinant DLK (MAP3K12) kinase and appropriate peptide substrates. Kinase activity is measured using radioactive ATP or fluorescence-based detection methods. The Ki value of 3 nM is determined from enzyme inhibition kinetics. Selectivity profiling against other kinases is performed to assess specificity. Assays are performed in triplicate with appropriate controls. CNS penetration is assessed using artificial membrane permeability assays or cell-based models.
|
| Cell Assay |
Cellular assays for DLK-IN-1 involve treating neuronal cell lines with varying concentrations of the compound (typically 0.001-10 microM range) for 24-72 hours. Readouts include assessment of DLK-mediated signaling pathways, neuronal survival, and axonal degeneration markers. Phosphorylation of DLK substrates is assessed by Western blotting. Neuroprotection assays evaluate the compound's ability to protect neurons from stress-induced cell death.
|
| Animal Protocol |
In vivo animal studies for DLK-IN-1 typically employ mouse models of Alzheimer's disease or other neurodegenerative conditions. Animals are administered DLK-IN-1 via oral gavage at various doses. Efficacy is assessed by measuring cognitive function, neuronal survival, and neuropathological markers. CNS penetration and target engagement are confirmed by measuring compound levels in brain tissue and assessing downstream biomarkers. Tolerability is evaluated through body weight and behavioral monitoring.
|
| ADME/Pharmacokinetics |
DLK-IN-1 is orally active with good pharmacokinetic properties. It maintains good penetration into the central nervous system. Following oral administration, the compound achieves appropriate brain concentrations for target engagement. PK parameters including half-life, Cmax, Tmax, AUC, and brain-to-plasma ratio are determined via LC-MS/MS analysis. The compound's CNS penetration supports its use in neurological disease research.
|
| Toxicity/Toxicokinetics |
DLK-IN-1 is well tolerated after intracerebral overdose. The compound shows good safety in preclinical models. As a research compound, standard safety precautions should be observed during handling including appropriate PPE and work in a fume hood. Comprehensive toxicology studies would be required for clinical development. The compound is for research use only. DLK-IN-1 is not approved for clinical use.
|
| References | |
| Additional Infomation |
DLK-IN-1 (CAS# 1620574-24-4) is a potent, selective, orally active DLK inhibitor. It has activity in Alzheimer's disease models. DLK is a key regulator of axonal degeneration, making DLK inhibitors potential therapeutic agents for neurodegenerative diseases. The compound maintains good CNS penetration and is well tolerated. DLK-IN-1 is not approved for clinical use and is for research purposes only. The compound is typically stored at -20degC.
|
| Molecular Formula |
C20H24F3N5O2
|
|---|---|
| Molecular Weight |
423.432074546814
|
| Exact Mass |
423.188
|
| CAS # |
1620574-24-4
|
| PubChem CID |
90292823
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.2
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
30
|
| Complexity |
622
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
FC(OC1=C(N)N=CC(=C1)C1C=C(C2[C@H]3CN(C4COC4)C[C@H]32)N(C(C)C)N=1)(F)F
|
| InChi Key |
UHEFRVBGJORHNV-UUVAVEHKSA-N
|
| InChi Code |
InChI=1S/C20H24F3N5O2/c1-10(2)28-16(18-13-6-27(7-14(13)18)12-8-29-9-12)4-15(26-28)11-3-17(19(24)25-5-11)30-20(21,22)23/h3-5,10,12-14,18H,6-9H2,1-2H3,(H2,24,25)/t13-,14+,18?
|
| Chemical Name |
5-[5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]-1-propan-2-ylpyrazol-3-yl]-3-(trifluoromethoxy)pyridin-2-amine
|
| 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 |
| 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) |
DMSO : ~62.5 mg/mL (~147.60 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3617 mL | 11.8083 mL | 23.6167 mL | |
| 5 mM | 0.4723 mL | 2.3617 mL | 4.7233 mL | |
| 10 mM | 0.2362 mL | 1.1808 mL | 2.3617 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
