Org 34167 (freebase)

Org 34167 freebase restores voltage dependence and reduces cation leak in homomeric HCN1^M305L channels, heterozygous HCN1^WT+M305L channels, and heterozygous channels expressing five additional HCN1 DEE variants in Xenopus laevis oocytes^[1].
Org 34167 freebase inhibits wild‑type human HCN1 channels expressed in Xenopus laevis oocytes via multiple mechanisms, including a dose‑dependent hyperpolarizing shift in the mid‑point voltage of activation (V_0.5, IC₅₀ = 331 μM), and a dose‑dependent change in effective valence (z, IC₅₀ = 219 μM)^[2].
Org 34167 freebase inhibits truncated human HCN1^WT-Δ channels expressed in Xenopus laevis oocytes via mechanisms independent of the CNBD^[2].
Org 34167 freebase modulates human HCN1 channel gating by altering the PD open-closed equilibrium (IC₅₀ = 7.9 μM), weakening VSD-PD coupling (IC₅₀ = 63 μM), and favoring inactive VSD states (IC₅₀ = 316 μM)^[2].
Org 34167 (compound 33) (0.1-1 mM; 4 h) freebase shows high permeability across Caco-2 cell monolayers with P_app,ab values of 1.42×10^-5 cm/s at 1 mM and 1.25×10^-5 cm/s at 0.1 mM, and permeability ratios < 2, indicating it is not a Pgp substrate in this system^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.