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Purity: ≥98%
LX2343, discovered by high throughout screening, is a small molecule compound that can effectively reverse the streptozocin (STZ)-induced neuronal apoptosis and tau hyperphosphorylation in vitro and in vivo. It exhibited moderate neuroprotective activities with the EC50 value of 15.8 μM. The neuroprotective effect of LX2343 was ascribed to its function in the inhibition of OS and tauopathy. LX2343 alleviated Aβ levels by both activating its clearance and inhibiting its production under STZ-induced pathological conditions. Moreover, assays in APP/PS1 transgenic AD model mice verified the amelioration of AD-relevant pathogenesis and cognitive deficits by LX2343. These results demonstrated that LX2343 was a multifunctional agent which exhibits potential capability for ameliorating multi-abnormalities of AD pathogenesis. However, the neuroprotective activity of LX2343 was a little weak and the structure-activity relationship (SAR) has not been studied yet. In order to search novel and more potent neuroprotective agent, LX2343 was chosen as the lead compound for further structural optimization.
| ln Vitro |
LX2343 (5–20 μM) promoted Aβ clearance in SH-SY5Y cells and primary astrocytes, while dose-dependently reducing Aβ accumulation in HEK293-APPsw and CHO-APP cells. LX2343 has the potential to treat AD since it improves cognitive impairment in APP/PS1 transgenic mice by both promoting clearance and inhibiting Aβ generation. LX2343 does not influence BACE1 protein levels, as shown by Western blot results in both HEK293-APPsw cells and CHO-APP cells. On the other hand, in vitro BACE1 enzymatic activity experiments showed that LX2343 dose-dependently reduces BACE1 activity (using TDC as a positive control) with an IC50 of 11.43±0.36 μM. We looked into the impact of ATP at various doses on the inhibitory action of LX2343 in order to determine whether competition exists between ATP and LX2343. The outcome showed that ATP had almost no effect on LX2343's inhibition of PI3K. This finding implies that LX2343 is a PI3K inhibitor that is non-ATP competitive. LX2343 exhibits an IC50 of 13.11±1.47 μM when exposed to 10 μM ATP, 13.86±1.12 μM when exposed to 50 μM ATP, and 15.99±3.23 μM when exposed to 100 μM ATP, according to reference [1].
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| ln Vivo |
A popular animal model for AD dementia is the APP/PS1 mouse, which expresses a mutant human presenilin 1 protein as well as a chimeric human Swedish mutant APP. We assess LX2343's ability to improve memory impairment in this model by administering the MWM test. The APP/PS1 transgenic mice's path lengths and escape latencies in the 8-day training trials are noticeably longer than those of the non-transgenic mice, and the administration of 10 mg/kg LX2343 clearly counteracts the longer path lengths and escape latencies at days 7 and 8. Compared to transgenic mice given a vehicle, LX2343-administered transgenic mice traverse the platform's hidden location more frequently in the probe trial assay[1].
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| References |
[1]. Guo XD, et al. Small molecule LX2343 ameliorates cognitive deficits in AD model mice by targeting both amyloid β production and clearance. Acta Pharmacol Sin. 2016 Sep;37(10):1281-1297
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| Molecular Formula |
C22H19CLN2O6S
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| Molecular Weight |
474.07
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| CAS # |
333745-53-2
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| SMILES |
ClC1C=CC(OC)=C(N(S(=O)(=O)C2C=CC=CC=2)CC(=O)NC2C=C3C(=CC=2)OCO3)C=1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.26 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 25.0 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: ≥ 2.5 mg/mL (5.26 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1094 mL | 10.5470 mL | 21.0939 mL | |
| 5 mM | 0.4219 mL | 2.1094 mL | 4.2188 mL | |
| 10 mM | 0.2109 mL | 1.0547 mL | 2.1094 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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LX2343 alleviated STZ-induced OS and ameliorated mitochondrial dysfunction.Acta Pharmacol Sin.2017Aug;38(8):1104-1119. |
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