Encukalner

Encukalner

Clinical data
Other names	XEN1101, azetukalner
Routes of administration	By mouth
Identifiers
IUPAC name N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide
CAS Number	1009344-33-5
PubChem CID	24743936
ChemSpider	62962263
UNII	91WL7OD122
KEGG	D12890
ChEMBL	ChEMBL5095264
Chemical and physical data
Formula	C23H29FN2O
Molar mass	368.496 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=CC(=CC(=C1NC(=O)CC(C)(C)C)C)N2CCC3=C(C2)C=CC(=C3)F
InChI 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) Key:FJNPZKZPWVVSON-UHFFFAOYSA-N

Encukalner also known as XEN1101 is an experimental small molecule anticonvulsant and selective K_v7.2/K_v7.3 potassium channel opener being investigated as a treatment for refractory focal onset seizures and major depressive disorder.

Mechanism of action

XEN1101 works by selectively opening the KCNQ2/3 (K_v7.2/K_v7.3) voltage-gated potassium channels via positive allosteric modulation. The opening of these voltage-gated potassium channels, which are critical regulators of neuronal excitability, leads to an increase in the flow of potassium ions out of neurons. The loss of positively charged potassium ions results in the inside of the neuron becoming negatively charged and hyperpolarized. This hyperpolarized resting state reduces the ability of the neuron to fire, thereby decreasing the likelihood of seizures.

This mechanism of action shares similarities with the medication retigabine, which was withdrawn from the market in 2017 due to its link to skin pigmentation and retinitis pigmentosa. XEN1101 has a different structure and does not appear to cause this effect or the development of the chromophoric phenazinium-type dimers that resulted in this side effect in retigabine.