Physicochemical Properties
| Molecular Formula | C28H27N7O |
| Molecular Weight | 477.560284852982 |
| Exact Mass | 477.227 |
| CAS # | 2409109-65-3 |
| PubChem CID | 148488346 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 3.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 36 |
| Complexity | 824 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C1(C2=CC=C3C(=C2)C=CC=C3)N(C2C=CN=C(N[C@H]3CCCN(C(C4CC4)=O)C3)N=2)C(CC#N)=CN=1 |
| InChi Key | MIFPZJRPCSILQA-QHCPKHFHSA-N |
| InChi Code | InChI=1S/C28H27N7O/c29-13-11-24-17-31-26(22-10-7-19-4-1-2-5-21(19)16-22)35(24)25-12-14-30-28(33-25)32-23-6-3-15-34(18-23)27(36)20-8-9-20/h1-2,4-5,7,10,12,14,16-17,20,23H,3,6,8-9,11,15,18H2,(H,30,32,33)/t23-/m0/s1 |
| Chemical Name | 2-[3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-naphthalen-2-ylimidazol-4-yl]acetonitrile |
| 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) |
Biological Activity
| ln Vitro | JNK3 inhibitor-4 (compound 15d) (1, 5, 10, 20 μM; 24 h or 48 h) prevents transported primary cortical neurons from being cytotoxically affected by Aβ1-42 [1]. 10 μM Aβ1-42 or 0.5 μM Anisomycin induces c-jun phosphorylation and APP phosphorylation in cortical neurons; JNK3 inhibitor-4 (50 μM; 4 10, 20 μM; 24 h, 48 h) blocks these processes [1]. h) The Caco-2 test revealed that it was highly permeable, and the PAMPA test indicated that it had blood-brain barrier (CNS+) permeability based on an effective permeability coefficient (Pe) > 4 [1]. JNK3 inhibitor-4 also has IC50 values of 5.78, 11.7, 15.1, 1.18, 3.10, 1.19, 0.280, 0.970, 0.860, and 0.340 μM, respectively, and inhibits GSK3α (h), GSK3β (h), JNK1, 2, MKK6, MOK, SAPK2a (h), SAPK2a (T106 M) (h), SAPK2b (h), MKK4, JNK1α1 (h), and JNK2α1 (h). |
| ln Vivo | JNK3 inhibitor-4 (compound 15d) can improve cognition in Alzheimer's disease models. JNK3 inhibitor-4 (10 mg/kg or 30 mg/kg; intravenous injection; 3 times a week for 1 month) exhibited substantial improvement in the Y maze test and mouse stirring test compared with the APP/PS1 drug-loaded group. Significantly improved spontaneous changes and delayed response behavior in mice (day 27 or 30), and showed model relevance [1] JNK3 inhibitor-4 (30 mg/kg; injected intravenously; single dose; recorded 0- 6h) showed blood-brain barrier permeability in SD tandem with a brain/vessel concentration ratio of 0.02 (26ng/g vs 1084). Pharmacokinetics in rats [1] Route dosage (mg/kg) AUC0-t (ng·h/mL) Cmax (ng/mL) Tmax (h) T1/2 (h) BA (% ng/mL) [1]. ) IV 1 718.0 0.22 PO 3 337.5 377.82 0.63 0.34 15.67 |
| Cell Assay |
Western Blot Analysis[1] Cell Types: Primary rat cortical neurons Tested Concentrations: 10 μM and 20 μM Incubation Duration: 24 Experimental Results: Monomeric Aβ1-42 induces c-jun phosphorylation in a dose-dependent manner and in a concentration-dependent manner Sexual mode is inhibited by JNK3 inhibitor 4. Cell viability assay[1] Cell Types: Primary rat cortical neurons Tested Concentrations: 1, 5, 10, 20 μM Incubation Duration: 24 hrs (hours) and 48 hrs (hours) Experimental Results: Displayed neuroprotection and increased cells under Aβ1-42 treatment vitality. |
| References |
[1]. Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease. Eur J Med Chem. 2023 Jan 5;245(Pt 1):114894. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0940 mL | 10.4699 mL | 20.9398 mL | |
| 5 mM | 0.4188 mL | 2.0940 mL | 4.1880 mL | |
| 10 mM | 0.2094 mL | 1.0470 mL | 2.0940 mL |