Org 34167 (freebase) 

Org 34167 freebase is a blood-brain barrier permeable HCN channel modulator. Org 34167 freebase possesses high Caco-2 cell permeability. Org 34167 freebase modulates HCN channel function to alter activation properties and suppress neuronal hyperexcitability. Org 34167 freebase induces tremors in mice at specific doses. Org 34167 freebase acts as a research tool for studies on developmental and epileptic encephalopathies as well as depression^[1][2][3].

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.

Org 34167 freebase (1-2 mg/kg; i.p.; single dose; 30 μM; bath application) significantly reduces epileptiform ECoG spiking frequency in Hcn1^M294L mice, normalizes select behavioral deficits, and rectifies biophysical and cellular hyperexcitability phenotypes in Hcn1^M294L neurons, while inducing tremors at therapeutic doses^[1].
Org 34167 freebase achieves good brain penetration in male Wistar rats, with a C_brain/C_blood ratio of 1.00^[3].

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

264.32

C₁₇H₁₆N₂O

198968-25-1

N[C@H](C1=C(C=CC=C1)C2=NOC3=CC=CC=C23)CC=C

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Bleakley LE, et al. Org 34167 rescues voltage dependence of mutant channels and normalizes hyperexcitability in HCN1 epilepsy. Epilepsia. 2025;66(12):5082-5095.

  [2]. McKenzie CE, et al. The Potential Antidepressant Compound Org 34167 Modulates HCN Channels Via a Novel Mode of Action. Mol Pharmacol. 2023;104(2):62-72.

  [3]. Faassen F, et al. Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003;263(1-2):113-122.  [Content Brief]