KCNQ2/3 activator-1 is an activator of Kv7.2/Kv7.3 (KCNQ2/3) potassium channels. KCNQ2/3 activator-1 may be used to relieve pain (a major medical problem) (information from patent WO2021113757A1, compound A).

Physicochemical Properties

Molecular Formula	C23H29FN2O
Molecular Weight	368.5
Exact Mass	368.226
Elemental Analysis	C, 74.97; H, 7.93; F, 5.16; N, 7.60; O, 4.34
CAS #	1009344-33-5
PubChem CID	24743936
Appearance	Off-white to gray solid powder
Density	1.1±0.1 g/cm3
Boiling Point	541.8±50.0 °C at 760 mmHg
Flash Point	281.4±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.579
LogP	5.28
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	505
Defined Atom Stereocenter Count	0
SMILES	FC1C=CC2=C(C=1)CCN(C1C=C(C)C(=C(C)C=1)NC(CC(C)(C)C)=O)C2
InChi Key	FJNPZKZPWVVSON-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H29FN2O/c1-15-10-20(11-16(2)22(15)25-21(27)13-23(3,4)5)26-9-8-17-12-19(24)7-6-18(17)14-26/h6-7,10-12H,8-9,13-14H2,1-5H3,(H,25,27)
Chemical Name	N-[4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide
Synonyms	Encukalner; XEN1101; XEN-1101 XEN 1101; 1OP 2198; VRX 621698; XPF-008;
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
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

References

1: Yang GM, Tian FY, Shen YW, Yang CY, Yuan H, Li P, Gao ZB. Functional characterization and in vitro pharmacological rescue of KCNQ2 pore mutations associated with epileptic encephalopathy. Acta Pharmacol Sin. 2023 Mar 17. doi: 10.1038/s41401-023-01073-y. Epub ahead of print. PMID: 36932231. 2: Elkommos S, Mula M. Current and future pharmacotherapy options for drug- resistant epilepsy. Expert Opin Pharmacother. 2022 Dec;23(18):2023-2034. doi: 10.1080/14656566.2022.2128670. Epub 2022 Sep 27. PMID: 36154780. 3: Bialer M, Johannessen SI, Koepp MJ, Levy RH, Perucca E, Perucca P, Tomson T, White HS. Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): II. Drugs in more advanced clinical development. Epilepsia. 2022 Nov;63(11):2883-2910. doi: 10.1111/epi.17376. Epub 2022 Aug 11. PMID: 35950617. 4: Biondi A, Rocchi L, Santoro V, Rossini PG, Beatch GN, Richardson MP, Premoli I. Spontaneous and TMS-related EEG changes as new biomarkers to measure anti- epileptic drug effects. Sci Rep. 2022 Feb 4;12(1):1919. doi: 10.1038/s41598-022-05179-x. PMID: 35121751; PMCID: PMC8817040. 5: Bialer M, Johannessen SI, Koepp MJ, Levy RH, Perucca E, Perucca P, Tomson T, White HS. Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). I. Drugs in preclinical and early clinical development. Epilepsia. 2020 Nov;61(11):2340-2364. doi: 10.1111/epi.16725. Epub 2020 Nov 14. PMID: 33190243. 6: Premoli I, Rossini PG, Goldberg PY, Posadas K, Green L, Yogo N, Pimstone S, Abela E, Beatch GN, Richardson MP. TMS as a pharmacodynamic indicator of cortical activity of a novel anti-epileptic drug, XEN1101. Ann Clin Transl Neurol. 2019 Nov;6(11):2164-2174. doi: 10.1002/acn3.50896. Epub 2019 Sep 30. PMID: 31568714; PMCID: PMC6856596. 7: Bialer M, Johannessen SI, Koepp MJ, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). I. Drugs in preclinical and early clinical development. Epilepsia. 2018 Oct;59(10):1811-1841. doi: 10.1111/epi.14557. PMID: 30368792.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~135.69 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.78 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	2.7137 mL	13.5685 mL	27.1370 mL
	5 mM	0.5427 mL	2.7137 mL	5.4274 mL
	10 mM	0.2714 mL	1.3569 mL	2.7137 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.