Natural/Endogenous Targets
Target 5-HT3A β2-adrenoceptor GABAA receptor α1 subunit GABAA receptor α2 subunit GABAA receptor α3 subunit GABAA receptor α4 subunit GABAA receptor α5 subunit GABAA receptor α6 subunit Glycine Receptor (All subtypes) glycine receptor α1 subunit glycine receptor α2 subunit glycine receptor α3 subunit glycine receptor β subunit GPR39 ZAC

Cofactor in Enzyme Reactions
Enzyme Reference geranylgeranyl diphosphate synthase 23 NG,NG-Dimethylarginine dimethylaminohydrolase 1 Endothelial NOS Inducible NOS Neuronal NOS 3-Mercaptopyruvate sulfurtransferase

Transporters Moving this Compound Across a Lipid Membrane
Transporter EC number Reaction Reference Solute carrier family 41 member 1 7

Selectivity at GPCRs
Key to terms and symbols		Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference β2-adrenoceptor Hs Allosteric modulator Positive 5.3 pKi - 20-21 ⤷ pKi 5.3 [20-21] β2-adrenoceptor Hs Allosteric modulator Negative 3.3 pKi - 20-21 ⤷ pKi 3.3 [20-21] GPR83 Mm Agonist Full agonist 5.0 pEC50 - 18 ⤷ pEC50 5.0 (EC50 1.02x10-5 M) [18] GPR39 Hs Agonist Agonist - - - 8 ⤷ [8]

Selectivity at ion channels
Key to terms and symbols		Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference Kir2.3 Hs Channel blocker Antagonist - - 5x10-5 - 3x10-4 4 ⤷ Conc range: 5x10-5 - 3x10-4 M [4] Voltage: -100.0 – 0.0 mV 5-HT3A Mm Allosteric modulator Biphasic - - 1x10-6 - 3x10-4 6,10 ⤷ Conc range: 1x10-6 - 3x10-4 M Positive (1-10μM): increased potency of 5-HT, decreased desensitization rate, reduced effect in the presence of Mg2+ or Ca2+. Negative (30-300μM). [6,10] Glycine Receptor (All subtypes) Hs Allosteric modulator Inhibition - - 1x10-5 14-15,17 ⤷ Conc range: 1x10-5 M [14-15,17] Glycine Receptor (All subtypes) Hs Allosteric modulator Potentiation - - 2x10-8 - 1x10-5 2,14-15,17 ⤷ Conc range: 2x10-8 - 1x10-5 M [2,14-15,17] Glycine Receptor (All subtypes) N/A Subunit-specific Inhibition - - < 1x10-6 16 ⤷ Conc range: < 1x10-6 M α1, α2 >> α1β, α2β [16] Glycine Receptor (All subtypes) N/A Subunit-specific Potentiation - - < 1x10-8 17 ⤷ Conc range: < 1x10-8 M α1, α1β > α2, α2β [17] glycine receptor α1 subunit Hs Allosteric modulator Potentiation 7.4 pEC50 - ⤷ pEC50 7.4 (EC50 3.7x10-8 M) endogenous; not affected by β subunit co-expression glycine receptor α2 subunit Hs Allosteric modulator Potentiation 6.3 pEC50 - ⤷ pEC50 6.3 (EC50 5.4x10-7 M) endogenous; not affected by β subunit co-expression ZAC Hs Agonist Agonist 3.3 – 3.7 pEC50 - 5,22 ⤷ pEC50 3.3 – 3.7 [5,22] TRPA1 Mm Activator Activation 2.3 pEC50 - 1,9 ⤷ pEC50 2.3 Zinc has similar activity at the human TRPA1 [1,9] Description: Calcium imaging Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglia neurons loaded with Fura-2 ASIC1 Hs Channel blocker - ~8.2 pIC50 - 3 ⤷ pIC50 ~8.2 (IC50 ~7x10-9 M) ASIC1a [3] TRPM1 Hs Channel blocker - 6.0 pIC50 - ⤷ pIC50 6.0 (IC50 1x10-6 M) TRPM2 Hs Channel blocker - 6.0 pIC50 - ⤷ pIC50 6.0 (IC50 1x10-6 M) Hv1 Hs Channel blocker - ~5.7 – 6.3 pIC50 - ⤷ pIC50 ~5.7 – 6.3 (IC50 ~2x10-6 – 5x10-7 M) glycine receptor α1 subunit Hs Allosteric modulator Inhibition 4.8 pIC50 - ⤷ pIC50 4.8 (IC50 1.5x10-5 M) endogenous glycine receptor β subunit Hs Allosteric modulator Inhibition 3.7 – 4.9 pIC50 - ⤷ pIC50 4.9 (IC50 1.3x10-5 M) endogenous; when co-expressed with the α1 subunit pIC50 3.7 (IC50 1.8x10-4 M) endogenous; when co-expressed with the α2 subunit ClC-4 Hs Channel blocker - 4.3 pIC50 - 19 ⤷ pIC50 4.3 (IC50 5x10-5 M) [19] Maxi Cl- Hs Channel blocker (extracellular Zn2+) - 4.3 pIC50 - 19 ⤷ pIC50 4.3 (IC50 5x10-5 M) [19] ASIC3 Hs Channel blocker - 4.2 pIC50 - 11 ⤷ pIC50 4.2 (IC50 6.1x10-5 M) [11] glycine receptor α3 subunit Hs Allosteric modulator Inhibition 3.8 pIC50 - ⤷ pIC50 3.8 (IC50 1.5x10-4 M) endogenous glycine receptor α2 subunit Hs Allosteric modulator Inhibition 3.4 pIC50 - ⤷ pIC50 3.4 (IC50 3.6x10-4 M) endogenous GABAA receptor α1 subunit Hs Allosteric modulator Inhibition - - - ⤷ GABAA receptor α2 subunit Hs Allosteric modulator Inhibition - - - ⤷ GABAA receptor α3 subunit Hs Allosteric modulator Inhibition - - - ⤷ GABAA receptor α4 subunit Hs Allosteric modulator Inhibition - - - ⤷ GABAA receptor α5 subunit Hs Allosteric modulator Inhibition - - - ⤷ GABAA receptor α6 subunit Hs Allosteric modulator Inhibition - - - ⤷ Kv12.1 Mm Gating inhibitor - - - - 24 ⤷ [24] Description: 1 mM Zn2+ slows activation 10-fold and shifts V0.5 for activation by ~+47 mV Conditions: Heterologous expression in Xenopus oocytes ClC-1 Hs Channel blocker - - - - ⤷ ClC-2 Hs Channel blocker - - - - ⤷

Additional information and targets (data relate to human unless otherwise stated)
Description	Data	Reference
Other channel blockers at TRPV5	Pb2+ = Cu2+ = Gd3+ > Cd2+ > Zn2+ > La3+ > Co2+ > Fe2

Targets where the ligand is described in the comment field
Target	Comment
GABAA receptor β1 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor β2 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor β3 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor γ2 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor γ3 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor α5 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor δ subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively
GABAA receptor α2 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor α1 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]
GABAA receptor α6 subunit	Diazepam and flunitrazepam are not active at channels containing this subunit. Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]. [3H]Ro154513 selectively labels α6-subunit and α4-subunit-containing receptors in the presence of a saturating concentration of a 'classical' benzodiazepine (e.g. diazepam). Sieghart et al. (2022) provides a review of the pharmacology of α6-containing GABAA receptors.
GABAA receptor α4 subunit	Diazepam and flunitrazepam are not active at this subunit. Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]. [3H]Ro154513 labels α4βγ2 and α6βγ2 receptors in the presence of a saturating concentration of a 'classical' benzodiazepine (e.g. diazepam).
GABAA receptor γ1 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13], So far, the only publication investigating the pharmacology of more than three or four ligands at γ1 receptors was Khom et al. (2006) [12].
GABAA receptor α3 subunit	Zn2+ is an endogenous allosteric regulator and causes potent inhibition of receptors formed from binary combinations of α and β subunits, incorporation of a δ or γ subunit causes a modest, or pronounced, reduction in inhibitory potency, respectively [13]

Ligand mentioned in the following text fields
Glycine receptors overview
ZAC overview
Acid-sensing (proton-gated) ion channels (ASICs) comments
Glycine receptors comments
Ionotropic glutamate receptors comments