| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| 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 |
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.
In rat brain slices, XE 991 dihydrochloride exhibits good in vivo efficacy and duration of action, with an EC50 of 490 nM for the increase of [3H]ACh release[2]. |
| ln Vivo |
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.
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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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| Additional Infomation |
XE991 belongs to the anthracene class of compounds.
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| Molecular Formula |
C26H20N2O
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|---|---|
| Molecular Weight |
449.37168
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| Exact Mass |
376.158
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| Elemental Analysis |
C, 82.95; H, 5.36; N, 7.44; O, 4.25
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| CAS # |
122955-42-4
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| Related CAS # |
XE991 dihydrochloride;122955-13-9
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| PubChem CID |
656732
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
625.3ºC at 760mmHg
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| Flash Point |
332ºC
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| Vapour Pressure |
6.84E-16mmHg at 25°C
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| LogP |
4.792
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
515
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C=CC(CC2(CC3C=CN=CC=3)C3C(=CC=CC=3)C(=O)C3=C2C=CC=C3)=CC=1
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| InChi Key |
KHJFBUUFMUBONL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H20N2O/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,17-18H2
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| Chemical Name |
10,10-bis(pyridin-4-ylmethyl)anthracen-9-one
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| Synonyms |
XE991; LS 190926; XE 991; LS-190926; XE-991; LS190926.
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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 | 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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