This potassium channel is a validated clinical target for partial onset seizures and is associated with a number of other childhood epilepsies; benign familial neonatal epilepsy and KCNQ2 encephalopathy, www.KCNQ2cure.org. KCNQ2/3 is the underlying ion channel of the M-current that is deactivated by muscarinic activation (Brown 1980; Guo 2003). KCNQ2/3 is inactivated by acetylcholine muscarinic activation and reactivation of the channel restores the M-current and protects against occurrence of seizures.
Mechanism of Action (MOA)
1OP-2198 is a positive allosteric potassium channel opener that targets the KCNQ2/3 transmembrane channel. As a positive allosteric modulator, 1OP-2198 enhances the ‘open’ configuration of the KCNQ potassium channel leading to modulation of neuronal activity (i.e., antiseizurogenic). KCNQ2/3 channels are ascribed as a neuronal brake and stabilize the resting membrane potential and reduce neuronal excitability.
Pharmacology, PK and GLP Toxicology of 1OP-2198
1OP-2198 was developed from a medicinal chemistry library of unique patent protected molecules. It was selected as the lead molecule due to its balance in potency, drug-ability and pharmacokinetic profile that improve upon the weaknesses of prior KCNQ2/3 (Kv7.2/7.3) compounds