| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
IC50: 17 nM (DLK), 40 nM (LZK)[1]
DN-1289 targets two kinases: dileucine zipper kinase (DLK) with an IC50 of 17 nM and leucine zipper-bearing kinase (LZK) with an IC50 of 40 nM. These kinases are involved in the MAPK signaling pathway and play a role in neuronal degeneration. |
|---|---|
| ln Vitro |
DN-1289 (Compound 14) (0.1, 0.3, and 1 μM; 0–20 h) inhibits the axonal degeneration of dorsal root ganglion (DRG) neurons caused by nerve growth factor (NGF) withdrawal [1]. In DRG neurons, NGF withdrawal-induced apoptotic protease activity is inhibited by DN-1289 (0.1, 0.3, and 1 μM; 0–20 h) [1].
In vitro, DN-1289 (Compound 14) inhibits the axonal degeneration of dorsal root ganglion (DRG) neurons caused by nerve growth factor (NGF) withdrawal at concentrations of 0.1, 0.3, and 1 μM. It also inhibits NGF withdrawal-induced apoptotic protease activity in DRG neurons. |
| ln Vivo |
In mouse models, DN-1289 (Compound 14) at doses of 100 mg/kg and 150 mg/kg administered intraperitoneally once daily for ten to fifteen days is well tolerated [1]. DN-1289 (150 mg/kg; oral; two doses per day for ten days) prevents the optic nerve crush (ONC) acute damage model from phosphorylating c-Jun [1]. Analysis of pharmacokinetics[1] Animal species Path Dosage (g/kg) plasma Cmax (micrometer) AUC0-24 h (μM·h) for plasma CLp (mL/min/kg) CLu (mL/min/kg) Vd (L/kg) t1/2 (h) F (%) Kpuu (AUC) hippocampus AUC0–2 (μM·h) mouse IV 1 1.06 4.06 8.6 200 4.7 6.8 / / / PO 3 0.58 3.9 / rat IV 1 1.09 2.42 14.7 150 6.7 6.5 / 0.6 4.05 10 2.32 21.9 / / / 7.9 56 0.4 6.91 PO 150 24.9 324 / / / 23.7 53 / / IP 100 15.4 280 / / / 23.7 53 / / cyno IV 0.5 0.746 2.79 6.1 64 3.4 7.9 / / /
In vivo, DN-1289 demonstrates neuroprotective effects in mouse models. At doses of 100 mg/kg and 150 mg/kg administered intraperitoneally once daily for 10-15 days, it is well tolerated. It prevents the phosphorylation of c-Jun in the optic nerve crush (ONC) acute damage model at 150 mg/kg (oral, twice daily for ten days). |
| Enzyme Assay |
Non-cellular kinase assays for DN-1289 involve measuring its inhibitory activity against purified DLK and LZK enzymes. The compound is incubated with the kinase and a substrate, and the inhibition of phosphorylation is quantified to determine the IC50 values of 17 nM for DLK and 40 nM for LZK.
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| Cell Assay |
In vitro cellular assays for DN-1289 are performed using dorsal root ganglion (DRG) neurons. The compound is tested for its ability to inhibit axonal degeneration and apoptosis induced by NGF withdrawal at concentrations of 0.1, 0.3, and 1 μM over a 20-hour period.
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| Animal Protocol |
In vivo animal experiments for DN-1289 involve administering the compound to mouse models of neurological injury. In the optic nerve crush model, the compound is given orally at 150 mg/kg twice daily for ten days to assess its ability to prevent c-Jun phosphorylation. In other models, it is given intraperitoneally at 100-150 mg/kg daily for 10-15 days to evaluate tolerability and neuroprotection.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties: DN-1289 has a favorable in vivo plasma half-life and blood-brain barrier (BBB) permeability. Detailed PK data from a mouse model shows that after intravenous (IV) administration at 1 mg/kg, the half-life (t1/2) is 6.8 hours. After oral (PO) administration at 3 mg/kg, the Cmax is 0.58 μM and the AUC0-24h is 3.9 μM·h.
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| Toxicity/Toxicokinetics |
Toxicological data for DN-1289 are limited. In mouse models, doses of 100 mg/kg and 150 mg/kg administered intraperitoneally once daily for 10-15 days are reported to be well tolerated. This suggests a favorable safety profile at these doses, but comprehensive toxicology studies would be required for full characterization.
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| References | |
| Additional Infomation |
DN-1289 has a molecular weight of 441.38 and a molecular formula of C18H19F4N7O2. Its CAS number is 3026597-15-6. It appears as a white to off-white solid powder and should be stored as a powder at -20°C. It is supplied for research purposes only.
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| Molecular Formula |
C18H19F4N7O2
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|---|---|
| Molecular Weight |
441.38
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| CAS # |
3026597-15-6
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| Appearance |
White to off-white solid powder
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| SMILES |
NC1=C(OC(F)F)N=C(C2=NC(N3[C@@H](C4)CO[C@@H]4C3)=NC(N5CCC(F)(F)C5)=C2)C=N1
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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: ~100 mg/mL (~226.6 mM; with ultrasonication and warming by heating to 60°C)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) 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.
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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.66 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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 3: ≥ 2.5 mg/mL (5.66 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2656 mL | 11.3281 mL | 22.6562 mL | |
| 5 mM | 0.4531 mL | 2.2656 mL | 4.5312 mL | |
| 10 mM | 0.2266 mL | 1.1328 mL | 2.2656 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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