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Chemical Structure| 122955-13-9 Chemical Structure| 122955-13-9

Structure of XE 991 2HCl
CAS No.: 122955-13-9

Chemical Structure| 122955-13-9

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XE991 2HCl is a potent and selective blocker of KV7 (KCNQ) voltage-gated potassium channels which blocks KV7.2+7.3 (KCNQ2+3) / M-currents (IC50 = 0.6 - 0.98 μM) and KV7.1 (KCNQ1) homomeric channels (IC50 = 0.75 μM) but is less potent against KV7.1/minK channels (IC50 = 11.1 μM).

Synonyms: XE 991 (hydrochloride); XE991 dihydrochloride; LS190926 dihydrochloride

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Product Details of XE 991 2HCl

CAS No. :122955-13-9
Formula : C26H22Cl2N2O
M.W : 449.37
SMILES Code : O=C1C2=C(C=CC=C2)C(CC3=CC=NC=C3)(CC4=CC=NC=C4)C5=CC=CC=C15.[H]Cl.[H]Cl
Synonyms :
XE 991 (hydrochloride); XE991 dihydrochloride; LS190926 dihydrochloride
MDL No. :MFCD09055426
InChI Key :WOGWMARIFDNZON-UHFFFAOYSA-N
Pubchem ID :45073462

Safety of XE 991 2HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Primary rat cortical neurons 300 nM 1 hour pretreatment, maintained for 24 hours To evaluate the neuroprotective effect of XE-991 against GA toxicity, results showed XE-991 significantly improved cell viability and reduced mitochondrial ROS production. Cell Death Discov. 2022 Sep 20;8(1):391
RA-differentiated SH-SY5Y cells 300 nM - 10 µM 1 hour pretreatment, maintained for 24 hours To evaluate the neuroprotective effect of XE-991 against GA-induced cell damage, results showed XE-991 significantly improved cell survival and reduced mitochondrial ROS production. Cell Death Discov. 2022 Sep 20;8(1):391
Primary rat microglia 30 µM 24 hours XE-991 blockade of Kv7/KCNQ channels exclusively inhibited the migratory capacity of resting microglia without affecting survival, proliferation, phagocytic capacity, or activation state. J Neuroinflammation. 2020 Apr 6;17(1):100

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague-Dawley rats Acute restraint stress model Bilateral PVN microinjection 0.5 pmol in 100 nl of aCSF Single injection XE-991 significantly increased plasma corticosterone levels, and acute stress attenuated the excitatory effect of XE-991 on plasma corticosterone levels. Neuropharmacology. 2017 Mar 1;114:67-76
Rats Hemorrhagic shock model Intravenous injection 1 mg/kg Single dose To evaluate the role of XE-991 in fluid resuscitation after hemorrhagic shock, results showed XE-991 significantly reduced the amount of fluid required for resuscitation J Biomed Sci. 2017 Jan 17;24(1):8
Sprague Dawley rats Rat mesenteric small arteries In vitro incubation 10 μmol/L Single dose, incubated for 30 minutes To investigate the role of Kv7 channels in the PVAT anticontractile effect, results showed that XE 991 reversed the noradrenaline-induced anticontractile effect by inhibiting Kv7 channels in PVAT. Br J Pharmacol. 2018 Sep;175(18):3685-3698
Rats Spontaneously hypertensive rats (SHRs) Microinjection into the central amygdala (CeA) 6.7 nmol Single injection, effects lasted for 26.8±3.9 minutes XE-991 increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in WKY rats but had no significant effect in SHRs. Cardiovasc Res. 2022 Jan 29;118(2):585-596
Borderline hypertensive rats (BHRs) Chronic unpredictable stress (CUS) model Bilateral microinjection into the CeA 6.7 nmol Single injection In unstressed BHRs, XE-991 increased sympathetic outflow and arterial blood pressure, but had no significant effect in CUS-treated BHRs. Cardiovasc Res. 2023 Jul 6;119(8):1751-1762

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.23mL

0.45mL

0.22mL

11.13mL

2.23mL

1.11mL

22.25mL

4.45mL

2.23mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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