EC18 HCN inhibitor is a HCN channel inhibitor. EC18 acts as a potent HCN4 inhibitor in a human iPSC-derived sinus node model with proven HCN4 expression. EC18 is an attractive pharmacological tool, enabling HCN channel-modulation studies with some specificity for HCN4 (EC50 [HCN4] = 3.98 ± 1.16 µM) over HCN1 (EC50 = 21.00 ± 3.98 µM) and HCN2 (EC50 = 19.35 ± 4.48 µM). EC18 abolishes HCN4 triggered pace making in a human iPSC (hiPSC) pacemaker model.

NUCC-0200590 is a small-molecule inhibitor of the TRIP8b-HCN interaction with IC50 of 7.0 uM in AlphaScreen assays, effectively disrupts the TRIP8b-HCN interaction in vitro and in vivo.

MS7710 is a brain-penetrant inhibitor targeting the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. MS7710 reduces the Ih current and decreases the activity of ventral tegmental area (VTA) dopamine neurons by inhibiting HCN channels. MS7710 can effectively improve social interaction deficits and reward-related cognitive flexibility in the chronic social defeat stress (CSDS) mouse model. MS7710 is promising for research of depression.

Org 34167 HCl salt is a broad-spectrum inhibitor of HCN channels with IC50 of 23.4, 8.2 and 9.2 uM for HCN1, HCN2 and HCN4 channels, respectively, slowing activation and causing a hyperpolarising shift in voltage-dependence of activation.

RO-275 is a potent, selective HCN1 ion channel inhibitor with IC50 of 46 nM, displays 311/100/302-fold selectivity over HCN2/HCN3/HCN4.

Zatebradine(UL-FS49) is a potent HCN channels antagonist, which decreased the heartbeat in a reversible manner; 92% inhibition of the hHCN1-mediated current at 10 uM.

Zatebradine hydrochloride is a bradycardic agent that creates use-dependent inhibition of hyperpolarization-activated current (If) in sinoatrial node cells (EC50 = 480 nM) and Purkinje fibres.