| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50:7.5 µM (Aβ1-40)[1]
The primary targets of QR-0217 are the amyloidogenic proteins amyloid-beta (Abeta1-40) and alpha-synuclein. The compound binds to soluble monomers or small oligomers of these pathological proteins, preventing their conversion into beta-sheet-rich aggregates that form amyloid plaques (in Alzheimer‘s disease) and Lewy bodies (in Parkinson's disease). The dual-target mechanism of QR-0217 addresses aggregation in both of these common protein misfolding disorders. |
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| ln Vitro |
Alpha-synuclein (4 µM) aggregation is inhibited by QR-0217 (20, 100 µM; 96 hours) [1]. Hippocampal slices from APP/PS1 transgenic mice with LTP impairment are greatly improved by QR-0217 (50 µM) [1].
In vitro, QR-0217 is a potent inhibitor of both Abeta1-40 aggregation and alpha-synuclein aggregation. The compound exhibits an IC50 of 7.5 uM for inhibition of Abeta1-40 aggregation, as measured in a thioflavin T (ThT)-based fluorescence assay. QR-0217 also blocks alpha-synuclein aggregation, though the precise IC50 for alpha-synuclein is not reported in the available references. This dual activity distinguishes QR-0217 from single-target amyloid inhibitors and makes it a versatile tool for neurodegeneration research. |
| ln Vivo |
In vivo, QR-0217 has been shown to reduce memory impairments caused by Abeta neurotoxicity in animal models. When administered to rodents with Abeta-induced cognitive deficits, the compound attenuates learning and memory dysfunction, likely by reducing the formation of toxic Abeta oligomers and aggregates. The exact doses and routes of administration used for in vivo efficacy studies are not provided in the available references, but the compound is active in Abeta neurotoxicity models.
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| Enzyme Assay |
A standard non-cellular assay for QR-0217 activity is the thioflavin T (ThT) fluorescence aggregation assay. Synthetic Abeta1-40 (25-50 uM) or alpha-synuclein (50-100 uM) is incubated with varying concentrations of QR-0217 (e.g., 0.1-100 uM) in PBS (pH 7.4) at 37degC with continuous agitation (for Abeta) or at 37degC quiescent (for alpha-synuclein). At defined time points (0, 6, 12, 24, 48, 72 hours), Thioflavin T is added, and fluorescence intensity (excitation 440 nm, emission 485 nm) is measured. The IC50 for inhibition of aggregation is calculated from the dose-response curve at the time point of maximal aggregation (typically 24-48 hours for Abeta1-40).
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| Cell Assay |
For cellular assays, neuronal cell lines (e.g., SH-SY5Y, PC12, or primary cortical neurons) are used. Pre-formed Abeta oligomers (5-20 uM) or alpha-synuclein aggregates are generated by incubating the peptides at 37degC for 24-48 hours. QR-0217 (e.g., 1-50 uM) is co-incubated with the aggregates or pre-treated with the cells. After 24-48 hours, cell viability is assessed by MTT or LDH release assays. The ability of QR-0217 to protect cells from aggregate-induced neurotoxicity is calculated as percent protection compared to vehicle control. Western blotting for markers of apoptosis (caspase-3, PARP) may also be performed.
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| Animal Protocol |
In an in vivo protocol, the Abeta neurotoxicity model is used. Male ICR or C57BL/6 mice are anesthetized, and aggregated Abeta1-40 or Abeta1-42 (5-10 ug/mouse) is injected intracerebroventricularly (ICV) to induce cognitive deficits. QR-0217 is administered orally or intraperitoneally (e.g., 5-30 mg/kg/day) for 7-14 days, beginning either before or after Abeta injection. Cognitive function is assessed using the Morris water maze (escape latency and probe trial performance) or passive avoidance test. A reduction in Abeta-induced memory impairment indicates the compound‘s in vivo efficacy.
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| Toxicity/Toxicokinetics |
Toxicological data for QR-0217 is not provided in the available references. As a research compound for laboratory use, the compound should be handled with standard laboratory safety precautions. Potential toxicity at high concentrations may include cellular stress or apoptosis in neuronal cell cultures, though the compound is intended for therapeutic research. The compound has been reported to reduce memory impairments, suggesting acceptable tolerability at effective doses in animal models.
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| References | |
| Additional Infomation |
QR-0217 is a unique dual-target research tool that inhibits both Abeta1-40 and alpha-synuclein aggregation, making it valuable for studying the overlapping pathological mechanisms of Alzheimer‘s disease and Parkinson's disease. Both of these neurodegenerative disorders are characterized by protein misfolding and aggregation (amyloid plaques in AD, Lewy bodies containing alpha-synuclein in PD). Single compounds that inhibit aggregation of both proteins may provide insights into common mechanisms of protein misfolding and potential therapeutics for multiple neurodegenerative diseases. The compound has an IC50 of 7.5 uM for Abeta1-40 and has been shown to reduce memory impairments caused by Abeta neurotoxicity, supporting its utility in preclinical models of Alzheimer's disease.
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| Molecular Formula |
C19H13NO3
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|---|---|
| Molecular Weight |
303.311424970627
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| Exact Mass |
303.089
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| CAS # |
1027786-12-4
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| PubChem CID |
24812734
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| Appearance |
Gray to dark gray solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
454
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC2=C(C=CC(=C2)O)C=C1C3=CNC4=C3C=C(C=C4)C(=O)O
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| InChi Key |
OPTWFLWYDUFHPL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H13NO3/c21-15-5-3-11-7-13(2-1-12(11)8-15)17-10-20-18-6-4-14(19(22)23)9-16(17)18/h1-10,20-21H,(H,22,23)
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| Chemical Name |
3-(6-hydroxynaphthalen-2-yl)-1H-indole-5-carboxylic acid
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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) |
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
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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 | 3.2970 mL | 16.4848 mL | 32.9696 mL | |
| 5 mM | 0.6594 mL | 3.2970 mL | 6.5939 mL | |
| 10 mM | 0.3297 mL | 1.6485 mL | 3.2970 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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