| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cl-NQTrp targets the aggregation of both amyloid-beta (Aβ) and tau proteins. These two proteins are the primary components of the pathological hallmarks of Alzheimer's disease: Aβ plaques and neurofibrillary tangles. By targeting both aggregation pathways, Cl-NQTrp has the potential to address multiple aspects of Alzheimer's disease pathology. The compound's dual-targeting mechanism distinguishes it from many other Alzheimer's disease therapeutics that target only one protein.
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| ln Vitro |
Using Cl-NQTrp, pre-formed PHF6 peptide fibrils were effectively disassembled[1]. PHF6 peptide oligomers may undergo structural modifications as a result of Cl-NQTrp[1].
In vitro, Cl-NQTrp has been shown to inhibit the aggregation of both Aβ and tau proteins. The compound's ability to target both aggregation pathways suggests it may have broad anti-aggregation activity. Standard in vitro assays include Thioflavin T fluorescence assays to measure amyloid fibril formation, circular dichroism spectroscopy to monitor protein conformational changes, and transmission electron microscopy to visualize fibril morphology. The compound's potency against Aβ and tau aggregation is determined by measuring the concentration required to inhibit fibril formation. |
| ln Vivo |
Since Cl-NQTrp targets both Aβ and tau aggregation, it may offer a novel therapeutic option for AD[2]. The shortened life span of htau-expressing flies is greatly reduced by Cl-NQTrp, resulting in 58% viability on day 29[2].
In vivo, Cl-NQTrp significantly alleviates the shorter life span of htau-expressing flies, leading to 58% viability on day 29. This demonstrates the compound's efficacy in a Drosophila model of tauopathy. The compound's ability to extend lifespan in this model suggests it may have neuroprotective effects. Cl-NQTrp could be a unique potential therapeutic for Alzheimer's disease since it targets aggregation of both Aβ and tau. Further in vivo studies in mammalian models would be needed to fully characterize its efficacy. |
| Enzyme Assay |
For non-cell-based receptor binding assays, Cl-NQTrp can be evaluated using purified Aβ and tau proteins. Aggregation assays are performed by incubating the proteins with increasing concentrations of the test compound under conditions that promote fibril formation. Thioflavin T fluorescence is measured to monitor fibril formation, and IC50 values for inhibition of aggregation are calculated. For binding studies, surface plasmon resonance or isothermal titration calorimetry can be used to measure the direct binding affinity of Cl-NQTrp to Aβ and tau monomers or oligomers.
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| Cell Assay |
For in vitro cellular assays, neuronal cell cultures or cells expressing tau or amyloid precursor protein are used. Cells are treated with Cl-NQTrp and protein aggregation is assessed using immunofluorescence with antibodies specific for aggregated Aβ or tau. Cell viability is measured using MTT or LDH assays to assess neuroprotection. For tauopathy models, cells expressing mutant tau are treated with the compound and tau aggregation is monitored. For Aβ toxicity models, cells are treated with exogenous Aβ in the presence or absence of the compound, and cell viability is assessed.
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| Animal Protocol |
Animal/Disease Models: Virgin females, carrying either the eye GMR -Gal4 driver or the pan-neuronal driver elavc155 -Gal4 on chromosome X, were collected and crossed with males carrying UAS-h tau on the 2nd chromosome or with wild-type Oregon- R (OR) males as a control[2].
Doses: 0.75 mg/mL. Route of Administration: Dripped every other day. Experimental Results: Inhibited PHF6 aggregation and ameliorates eye neurodegeneration Drosophila overexpressing the human tau protein (htau). For in vivo animal studies, Cl-NQTrp can be administered to Drosophila models of tauopathy or Alzheimer's disease via dietary supplementation. In these models, lifespan is monitored, and protein aggregation is assessed using immunohistochemistry. In mammalian models, the compound can be administered via intraperitoneal injection or oral gavage. Behavioral tests, brain tissue analysis for Aβ and tau aggregates, and assessment of neuroinflammation markers are performed. Dosing regimens vary depending on the specific model and study objectives. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Cl-NQTrp have not been extensively characterized. The compound has a molecular weight of 331.83 and a molecular formula of C18H10ClN3O2. Based on its molecular properties, the compound is expected to have moderate lipophilicity and good blood-brain barrier penetration, which is essential for targeting Aβ and tau aggregation in the brain. Comprehensive ADME studies would be needed for full pharmacokinetic characterization, including assessment of oral bioavailability, half-life, protein binding, and tissue distribution.
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| Toxicity/Toxicokinetics |
The toxicity profile of Cl-NQTrp has not been extensively reported. The compound is for research use only and not for human consumption. Standard toxicological evaluation would include acute and repeated-dose toxicity studies, as well as assessment of effects on the central nervous system. Given its mechanism as an inhibitor of protein aggregation, potential off-target effects on normal protein homeostasis would be a consideration. The compound's safety profile in Drosophila models appears favorable, as it extended lifespan without obvious toxicity.
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| References |
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| Additional Infomation |
Cl-NQTrp is a compound that targets aggregation of both Aβ and tau, making it a unique potential therapeutic for Alzheimer's disease. It significantly alleviates the shorter life span of htau-expressing flies, leading to 58% viability on day 29. The compound's dual-targeting mechanism distinguishes it from many other Alzheimer's disease therapeutics that target only one protein. It is available for research purposes only and has not been approved for clinical use.
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| Molecular Formula |
C21H15N2O4CL
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| Molecular Weight |
394.808
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| Exact Mass |
394.072
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| CAS # |
185351-23-9
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| PubChem CID |
1427125
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
707
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C(=O)C2C(=CC=CC=2)C(=O)C=1N[C@H](C(O)=O)CC1C2=C(C=CC=C2)NC=1
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| InChi Key |
ZKNQSBBALRSDBQ-INIZCTEOSA-N
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| InChi Code |
InChI=1S/C21H15ClN2O4/c22-17-18(20(26)14-7-2-1-6-13(14)19(17)25)24-16(21(27)28)9-11-10-23-15-8-4-3-5-12(11)15/h1-8,10,16,23-24H,9H2,(H,27,28)/t16-/m0/s1
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| Chemical Name |
(2S)-2-[(3-chloro-1,4-dioxonaphthalen-2-yl)amino]-3-(1H-indol-3-yl)propanoic 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) |
DMSO: 250 mg/mL (633.22 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: ≥ 2.08 mg/mL (5.27 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5329 mL | 12.6643 mL | 25.3286 mL | |
| 5 mM | 0.5066 mL | 2.5329 mL | 5.0657 mL | |
| 10 mM | 0.2533 mL | 1.2664 mL | 2.5329 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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