| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ARN-1468 targets SERPINA3 (with an ITC-measured KD of 26 uM) and SerpinA3n. It inhibits the activity of these serpins, which would otherwise inhibit proteases. By freeing these proteases, ARN-1468 enhances the degradation of pathological prion protein (PrPᶜ).
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| ln Vitro |
ARN-1468 is a cellular-active small molecule that decreases prion accumulation. In ScGT1 and ScN2a cell lines infected with different prion strains (RML, 22L), ARN-1468 demonstrates pronounced anti-prion effects with EC50 values of 8.64, 19.3, 11.2, and 6.27 uM, respectively. It does not affect normal PrPᶜ metabolism.
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| ln Vivo |
In male C57BL/6 mice, ARN1468 (Compound 5) (3 mg/kg IV; 10 mg/kg PO; once) exhibits low brain concentrations and high plasma clearance [1].
ARN-1468 (3 mg/kg, IV; 10 mg/kg, PO; once) reveals low brain concentrations and high plasma clearance in male C57BL/6 mice. The compound shows synergy with quinacrine to clear prions in ScN2a RML cells. Further in vivo efficacy studies in prion-infected animals are ongoing. |
| Enzyme Assay |
For cell-free binding assays, SERPINA3 protein is titrated into a solution of ARN-1468 (e.g., 100 uM) at 25degC in a suitable buffer. The heat change from the interaction is measured by Isothermal Titration Calorimetry (ITC), and the data are fitted to determine the KD, binding stoichiometry (N), and thermodynamic parameters (deltaH, deltaS).
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| Cell Assay |
ScGT1 or ScN2a cells chronically infected with prions (RML or 22L strains) are seeded in 96-well plates and treated with ARN-1468 (0.1-50 uM) for 72-96 hours. After treatment, cells are lysed, and the levels of pathological scrapie prion protein (PrPᶜ) are quantified by ELISA or Western blot following proteinase K digestion. Cell viability is assessed by MTT or CellTiter-Glo.
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| Animal Protocol |
The primary in vivo model is chronic prion-infected mice (e.g., RML or 22L strain). ARN-1468 is administered orally or intraperitoneally (e.g., daily or twice weekly) starting at a predetermined time post-inoculation, either alone or in combination with quinacrine. The primary endpoints are survival time and clinical signs of disease, which are monitored daily.
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| ADME/Pharmacokinetics |
Following intravenous administration (3 mg/kg) in male C57BL/6 mice, ARN-1468 is rapidly cleared from plasma, resulting in low systemic and brain concentrations. Its oral bioavailability is low. For in vitro use, it is soluble in DMSO (10 mM). Storage: powder at -20degC for 3 years; in solvent at -80degC for 1 year.
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| Toxicity/Toxicokinetics |
Standard safety precautions for research chemicals apply. ARN-1468 is for research use only, not for human consumption. Avoid inhalation, ingestion, and skin contact. Use personal protective equipment.
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| References |
[1]. Colini Baldeschi A, et al. Innovative Non-PrP-Targeted Drug Strategy Designed to Enhance Prion Clearance. J Med Chem. 2022 Jun 30.
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| Additional Infomation |
ARN-1468 (compound 5) is a research-grade anti-prion agent. It represents a first-in-class approach for treating prion diseases by targeting serpins rather than the prion protein directly. Chemical formula: C16H17F3N4O2; molecular weight: 354.33. Purity: ≥98%. Store at -20degC.
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| Molecular Formula |
C16H17F3N4O2
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|---|---|
| Molecular Weight |
354.33
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| Exact Mass |
354.13
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| CAS # |
1381459-14-8
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| PubChem CID |
92570374
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
463
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CNCCC1C(=O)C2=C(N(N=C2)C3=CC=C(C=C3)OC(F)(F)F)N
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| InChi Key |
OOUGXIZAHWLQEM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H17F3N4O2/c17-16(18,19)25-12-3-1-11(2-4-12)23-15(20)13(9-22-23)14(24)10-5-7-21-8-6-10/h1-4,9-10,21H,5-8,20H2
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| Chemical Name |
[5-amino-1-[4-(trifluoromethoxy)phenyl]pyrazol-4-yl]-piperidin-4-ylmethanone
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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 : ~5.56 mg/mL (~15.69 mM)
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| 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 | 2.8222 mL | 14.1111 mL | 28.2223 mL | |
| 5 mM | 0.5644 mL | 2.8222 mL | 5.6445 mL | |
| 10 mM | 0.2822 mL | 1.4111 mL | 2.8222 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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