RO-275

RO-275 is a potent, selective, and brain-penetrant small molecule inhibitor of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) with an IC50 of 46 nM. Developed by Roche and distributed in collaboration with the Structural Genomics Consortium (SGC), RO-275 exhibits high selectivity (>100-fold) over other HCN isoforms (HCN2, HCN3, and HCN4) and shows no significant activity against other ion channels such as hERG and Nav1.5. In vivo, RO-275 has been shown to improve working memory performance in rodent models without affecting cardiac physiology or heart rate, highlighting its potential as a research tool and therapeutic candidate for cognitive dysfunction associated with neurological and psychiatric disorders.

Other names

4-((2-Chloro-3-methylpyridin-4-yl)ethynyl)-5-methyl-1-(pyridin-3-yl)-1H-imidazole-2-carboxamide