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| 5mg |
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Purity: ≥98%
XE991 diHCl (LS190926) is a novel, potent and selective blocker of KCNQ (Kv7) voltage-gated potassium channels. XE991 blocks KCNQ2+3/M-currents (IC50 = 0.6-0.98 μM) and KCNQ1 homomeric channels (IC50 = 0.75 μM) but is less potent against KCNQ1/minK channels (IC50 = 11.1 μM).
XE991 (chemical name: 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone, LS190926, commonly used as dihydrochloride salt) is a potent and selective Kv7 (KCNQ) potassium channel blocker, also well-known as an M-current inhibitor. It not only blocks the neuronal M-channels formed by KCNQ2/KCNQ3 heterotetramers but also effectively inhibits KCNQ1 (KvLQT1) channels. Initially developed as a cognitive enhancer due to its ability to enhance neuronal excitability and firing frequency, XE991 serves as a key pharmacological tool in electrophysiological studies to distinguish the functions of different types of potassium channels.| Targets |
The primary targets of XE991 are members of the Kv7 potassium channel family (KCNQ1-5), particularly with high affinity for homomeric or heteromeric tetramers composed of KCNQ2 and KCNQ3 subunits. It can also effectively block KCNQ1 channels. However, when KCNQ1 co-assembles with the minK (KCNE1) accessory subunit to form the cardiac slow delayed rectifier potassium channel (IKs), the sensitivity to XE991 is significantly reduced. XE991 also acts on cAMP-sensitive potassium channels (KCNQ1/KCNE3 complexes) in certain epithelial tissues. Furthermore, studies suggest that Kv7 channel blockade mediates XE991-induced vasodilation in certain cell types, indicating potential effects on Kv7.4/Kv7.5 channels as well.
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| ln Vitro |
XE991 diHClide exhibits good in vivo efficacy and duration of action, stimulates [3H]ACh release in rat brain slices, and has an EC50 of 490 nM [2].
In vitro, XE991 is a highly effective potassium channel blocker. In Xenopus oocyte expression systems, its IC50 values for KCNQ2, KCNQ3, and KCNQ2/KCNQ3 heteromeric channels are 0.71 μM, 0.98 μM, and 0.6 μM, respectively; the IC50 for KCNQ1 is 0.75 μM. When KCNQ1 co-expresses with minK to form IKs channels, the blocking potency decreases by approximately 14- to 18-fold, with the IC50 value rising to 11.1 μM. In rat brain slices, XE991 enhances [3H]ACh release in a concentration-dependent manner, with an EC50 of 490 nM. At the cellular level, XE991 can block potassium channels on the basolateral membrane of epithelial cells, thereby inhibiting chloride secretion. |
| ln Vivo |
In vivo studies demonstrate that XE991 can effectively penetrate the blood-brain barrier and modulate central neuronal activity. In rats, intraperitoneal injection of XE991 (3 mg/kg) significantly enhances burst firing of midbrain dopamine neurons and increases the proportion of short interspike intervals within spike trains. In brain slice experiments, XE991 blocks the M-current, triggering high-frequency burst firing in hippocampal CA1 pyramidal neurons and significantly increasing action potential firing frequency. In vascular function studies, XE991 attenuates GoSlo-SR compound-induced vasodilation, indicating a role for Kv7 channels in regulating vascular tone.
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| Enzyme Assay |
A standard workflow for target validation of XE991 involves two-electrode voltage-clamp electrophysiology using a heterologous expression system in Xenopus oocytes. The procedure is as follows: cRNA encoding the target channel is injected into Xenopus oocytes, which are then cultured for 1-5 days to express functional channels. Whole-cell currents are recorded using a two-electrode voltage-clamp amplifier at room temperature. Cells are held at a holding potential of -80 mV, and depolarizing pulses are applied to activate potassium currents. XE991 is applied via perfusion. Current amplitudes before and after drug application are measured, and the percentage of inhibition is calculated. A concentration-inhibition curve is then fitted to determine the IC50 value.
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| Cell Assay |
A representative in vitro cellular assay uses CHO-K1 cells stably expressing KCNQ1/KCNE1 channels for thallium flux-based fluorescence detection. The workflow is as follows: Cells are seeded and cultured overnight. Following medium removal, FluxOR thallium-sensitive fluorescent dye solution is added. After incubation, the dye is removed and assay buffer is added, followed by different concentrations of XE991. After a second incubation, the cell plate is loaded onto a kinetic imaging plate reader. Stimulus buffer containing thallium is then added to initiate channel opening, and fluorescence signals are recorded. The fluorescence ratio is calculated to evaluate the inhibitory effect of XE991 on channel activity.
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| Animal Protocol |
A classic in vivo workflow to assess the effects of XE991 on central neuronal electrical activity is as follows: Adult rats are anesthetized and undergo craniotomy. Dopamine neurons in the substantia nigra pars compacta or ventral tegmental area are recorded using tungsten microelectrodes or glass micropipettes. After stable baseline firing is recorded, XE991 is administered intraperitoneally at a dose of 3 mg/kg. Changes in firing frequency and pattern are continuously recorded post-administration, with particular attention to the proportion of burst firing and the distribution of interspike intervals. Data analysis involves identifying and counting burst firing events using dedicated software to assess the degree of enhanced neuronal excitability induced by XE991.
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| ADME/Pharmacokinetics |
Systematic pharmacokinetic data (such as half-life, volume of distribution, bioavailability, and plasma protein binding) for XE991 are limited in publicly available literature. Current information indicates that XE991 can be effectively administered in vivo via intraperitoneal injection and acts on the central nervous system, suggesting it possesses good blood-brain barrier penetration capability. In vitro studies show that XE991 has a sustained effect in brain tissue, such as continuously enhancing acetylcholine release in rat brain slices. Detailed absorption, distribution, metabolism, and excretion data require further elucidation.
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| Toxicity/Toxicokinetics |
According to the Safety Data Sheet, XE991 dihydrochloride is a potentially toxic active pharmaceutical ingredient. It is classified as "Very toxic if swallowed" (R28) and carries potential risks of impaired fertility (R62) and harm to the unborn child (R63). It is also irritating to the skin (R38), poses a risk of serious damage to eyes (R41), and long-term exposure may cause serious damage to health (R48). Therefore, all experimental manipulations involving XE991 must be performed by trained personnel in a fume hood with strict adherence to personal protective measures, including wearing lab coats, chemical-resistant gloves, and eye/face protection. In case of skin or eye contact, immediately flush with copious amounts of water and seek medical advice.
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| References |
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| Molecular Formula |
C26H22CL2N2O
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| Molecular Weight |
449.371684551239
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| Exact Mass |
448.11
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| CAS # |
122955-13-9
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| Related CAS # |
XE991;122955-42-4
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| PubChem CID |
45073462
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.396
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
515
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.O=C1C2C=CC=CC=2C(CC2C=CN=CC=2)(CC2C=CN=CC=2)C2C=CC=CC=21
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| InChi Key |
WOGWMARIFDNZON-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H20N2O.2ClH/c29-25-21-5-1-3-7-23(21)26(17-19-9-13-27-14-10-19,18-20-11-15-28-16-12-20)24-8-4-2-6-22(24)25/h1-16H,17-18H22*1H
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| Chemical Name |
10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone, dihydrochloride
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| Synonyms |
XE991 XE 991 XE-991 LS 190926 LS190926 LS-190926.
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ~11.11 mg/mL (~24.72 mM)
DMSO : ~7.14 mg/mL (~15.89 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.71 mg/mL (1.58 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 7.1 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: ≥ 0.71 mg/mL (1.58 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 7.1 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. View More
Solubility in Formulation 3: ≥ 0.71 mg/mL (1.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2253 mL | 11.1267 mL | 22.2534 mL | |
| 5 mM | 0.4451 mL | 2.2253 mL | 4.4507 mL | |
| 10 mM | 0.2225 mL | 1.1127 mL | 2.2253 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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