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).

Physicochemical Properties

Molecular Formula	C26H22CL2N2O
Molecular Weight	449.37168
Exact Mass	448.11
CAS #	122955-13-9
Related CAS #	XE991;122955-42-4
PubChem CID	45073462
Appearance	Off-white to light yellow solid powder
LogP	6.396
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	515
Defined Atom Stereocenter Count	0
InChi Key	WOGWMARIFDNZON-UHFFFAOYSA-N
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
Chemical Name	10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone, dihydrochloride
Synonyms	XE991 XE 991 XE-991 LS 190926 LS190926 LS-190926.
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].

References

[1]. Two new potent neurotransmitter release enhancers, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone and 10,10-bis(2-fluoro-4-pyridinylmethyl)-9(10H)-anthracenone: comparison to linopirdine. J Pharmacol Exp Ther. 1998 May;285(2):724-30. PMID: 9580619. [2]. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998 Dec 4;282(5395):1890-3. [3]. Two new potent neurotransmitter release enhancers, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone and 10,10-bis(2-fluoro-4-pyridinylmethyl)-9(10H)-anthracenone: comparison to linopirdine. J Pharmacol Exp Ther. 1998 May;285(2):724-30.

Solubility Data

Solubility (In Vitro)

H2O : ~11.11 mg/mL (~24.72 mM) DMSO : ~7.14 mg/mL (~15.89 mM)

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. 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. 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 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	2.2253 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.