Org 34167

Org 34167 is a brain-penetrant, broad-spectrum hyperpolarization-activated cyclic nucleotide-gated (HCN) channel inhibitor. Originally developed by Organon Laboratories (later acquired by Merck & Co.) for the treatment of depression, it successfully completed Phase I clinical trials where it was found to be well-tolerated in humans. More recently, Org 34167 has been investigated as a potential precision medicine for developmental and epileptic encephalopathy (DEE) caused by pathogenic variants in the HCN1 gene (HCN1-DEE). It acts by restoring the voltage sensitivity of mutated HCN1 channels, thereby reducing the pathological cation leak and suppressing neuronal hyperexcitability. However, its broad-spectrum inhibition of HCN channels (including HCN2) is associated with the emergence of tremors at therapeutic doses.

Other names

(1S)-1-(2-(1,2-benzoxazol-3-yl)phenyl)but-3-en-1-amine(S)-1-(2-(benzo[d]isoxazol-3-yl)phenyl)but-3-en-1-amine(S)-2-(1,2-benzisoxazol-3-yl)-alpha-(2-propenyl)benzenemethanaminepropyl-1,2 benzisoxazole derivative