Target family: Cyclic nucleotide-regulated channels (CNG) (type: vgic)
Target: HCN2

Ligand: cilobradine (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 5.099999904632568 pIC50
Reference (Journal): Bradycardic and proarrhythmic properties of sinus node inhibitors.
Published in: Mol Pharmacol

Ligand: clonidine (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: FDA (1974)
Primary target: no
Median affinity: 5.090000152587891 pIC50
Reference (Journal): Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine.
Published in: Circulation

Ligand: Cs+ (Inorganic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 3.700000047683716 pIC50
Reference (Journal): Functional expression of the human HCN3 channel.
Published in: J Biol Chem

Ligand: cyclic AMP (Metabolite)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Median affinity: 6.3 pKi
Reference (Journal): A family of hyperpolarization-activated mammalian cation channels.
Published in: Nature

Ligand: cyclic CMP (Synthetic organic)
Interaction type: Activator
Action: None
Ligand approved: no
Median affinity: 4.52 pEC50
Reference (Journal): Regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity by cCMP.
Published in: J Biol Chem

Ligand: cyclic GMP (Metabolite)
Interaction type: Activator
Action: Agonist
Ligand approved: no
Median affinity: 5.2 pKi
Reference (Journal): A family of hyperpolarization-activated mammalian cation channels.
Published in: Nature

Ligand: EC18 (Synthetic organic)
Interaction type: Channel blocker
Action: None
Ligand approved: no
Primary target: no
Median affinity: 4.710000038146973 pEC50
Reference (Journal): Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue.
Published in: Br J Pharmacol

Ligand: ivabradine (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: yes
Approval source: EMA (2005), FDA (2015)
Primary target: no
Median affinity: 5.599999904632568 pIC50
Reference (Journal): Bradycardic and proarrhythmic properties of sinus node inhibitors.
Published in: Mol Pharmacol

Ligand: MEL57A (Synthetic organic)
Interaction type: Channel blocker
Action: None
Ligand approved: no
Primary target: no
Median affinity: 4.900000095367432 pEC50
Reference (Journal): Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue.
Published in: Br J Pharmacol

Ligand: Mg2+ (Inorganic)
Interaction type: Channel blocker
Action: None
Ligand approved: no
Median affinity: 3.2 pIC50
Reference (Journal): Intracellular Mg2+ is a voltage-dependent pore blocker of HCN channels.
Published in: Am J Physiol, Cell Physiol

Ligand: PIP2 (Metabolite)
Interaction type: Activator
Action: None
Ligand approved: no
Median affinity: 4.96 pEC50
Reference (Journal): Regulation of gating and rundown of HCN hyperpolarization-activated channels by exogenous and endogenous PIP2.
Published in: J Gen Physiol

Ligand: zatebradine (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: no
Median affinity: 5.7 pIC50
Reference (Journal): Bradycardic and proarrhythmic properties of sinus node inhibitors.
Published in: Mol Pharmacol

Ligand: ZD7288 (Synthetic organic)
Interaction type: Channel blocker
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 4.400000095367432 pIC50
Reference (Journal): Functional expression of the human HCN3 channel.
Published in: J Biol Chem