Mibefradil dihydrochloride

SKU: orb1309424

Description

Mibefradil dihydrochloride is a calcium channel blocker exhibiting moderate selectivity for T-type over L-type channels (IC50s of 2.7 μM and 18.6 μM, respectively). It is a research tool used in cardiovascular and neurological studies, with applications in both in vitro electrophysiology and in vivo models of hypertension and arrhythmia.

Research Area

Metabolism Research, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 116666-63-8
• MW: 568.55
• Purity: 99.91% (May vary between batches)
• Formula: C₂₉H₄₀Cl₂FN₃O₃
• SMILES: Cl.Cl.COCC(=O)O[C@]1(CCN(C)CCCc2nc3ccccc3[nH]2)CCc2cc(F)ccc2[C@@H]1C(C)C
• Target: Calcium Channel
• Solubility: H2O:122 mg/mL (214.58 mM)

Bioactivity

• Target IC50:
  Ca2+ channel, T-type:2.7 μM |Ca2+ channel, L-type:18.6 μM
• In Vivo:
  Compared with the saline-treated group, rats receiving Mibefradil or Ethosuximide show significant lower CaV3.2 expression in the spinal cord and DRG.
• In Vitro:
  Mibefradil dihydrochloride inhibits reversibly the T- and L-type currents with IC50 values of 2.7 and 18.6 μM, respectively..Mibefradil inhibited Orai1, Orai2, and Orai3 currents dose-dependently. The IC50 for Orai1, Orai2, and Orai3 channels was 52.6, 14.1, and 3.8 μM respectively. Outside-out patch demonstrated that perfusion of 10-μM mibefradil to the extracellular surface completely blocked Orai3 currents and single channel activity evoked by 2-APB. Intracellular application of mibefradil did not alter Orai3 channel activity. Mibefradil at higher concentrations (>50 μM) inhibited Ca2+ release but had no effect on cytosolic STIM1 translocation evoked by thapsigargin. Inhibition on Orai channels by mibefradil was structure-related, as other T-type Ca2+ channel blockers with different structures, such as ethosuximide and ML218, had no or minimal effects on Orai channels. Moreover, mibefradil inhibited cell proliferation, induced apoptosis, and arrested cell cycle progression.
• Cell Research:
  Human Orai1-3 cDNAs in tetracycline-regulated pcDNA4/TO vectors were transfected into HEK293 T-REx cells with stromal interaction molecule 1 (STIM1) stable expression. The Orai currents were recorded by whole-cell and excised-membrane patch clamp. Ca2+ influx or release was measured by Fura-PE3/AM. Cell growth and death were monitored by WST-1, LDH assays and flow cytometry.

Storage & Handling

• Storage: keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Ca channels, Ca2+ channels, Calcium Channel, CalciumChannel, Inhibitor, inhibit, Mibefradil, Mibefradil dihydrochloride, Mibefradil Dihydrochloride, L-type calcium channel, T-type calcium channel, Ro 40-5967, Ro 40-5967 (dihydrochloride)

Compound Identifiers

PubChem CID

60662