Senicapoc

SKU: orb1304118

Description

Senicapoc (ICA-17043) is a potent Gardos channel inhibitor with low nanomolar IC50 values, effectively preventing calcium-induced potassium efflux and red blood cell dehydration in vitro. It has demonstrated therapeutic potential in preclinical models for sickle cell disease by ameliorating RBC pathology.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 289656-45-7
• MW: 323.34
• Purity: 99.50% (May vary between batches)
• Formula: C₂₀H₁₅F₂NO
• SMILES: NC(=O)C(c1ccccc1)(c1ccc(F)cc1)c1ccc(F)cc1
• Target: Potassium Channel
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (6.19 mM);DMSO:50 mg/mL (154.64 mM)

Bioactivity

• Target IC50:
  RBC:30 ± 20 nM|RBCs (human):11 ± 2 nM
• In Vivo:
  ICA-17043 (10 mg/kg, p.o.) administration produces a significant decrease in Gardos channel activity measured at day 11 and 21 and is associated with a corresponding increase in red cell K+ content without changes in Na+ content. ICA-17043 (10 mg/kg, twice a day) induces a significant increase in Hct after 11 days of dosing in the SAD mouse. Senicapoc (30 mg/kg, p.o.) reduces airway hyperresponsiveness, eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and vascular remodelling in the sheep.
• In Vitro:
  ICA-17043 is shown to block the Gardos channel of mouse (C57 Black) RBCs with an IC50 of 50±6 nM. ICA-17043 blocks this increase in cellular hemoglobin concentration in human RBCs in a concentration-dependent fashion.
• Cell Research:
  Senicapoc is dissolved in DMSO or 100% ethanol. The whole blood is initially diluted 1:1 with Modified Flux Buffer (MFB), consisting of 140 mM NaCl, 5 mM KCl, 10 mM Tris (tris(hydroxymethyl)aminomethane), 0.1 mM EGTA (ethyleneglycoltetraacetic acid) (pH=7.4). The blood is centrifuged at 1000 rpm, and the pellet comprised primarily of RBCs is washed 3 times with MFB. The cells are then loaded with 86Rb+ by incubating the washed cells with 86Rb+ at a final concentration of 0.185 MBq/mL (5 μCi/mL) in MFB for at least 3 hours at 37°C. After loading with 86Rb+, the RBCs are washed 3 times with chilled MFB. The cells are then incubated for 10 minutes with test compound (senicapoc) at concentrations that ranged from 1 nM to 10 000 nM. Efflux of 86Rb+ is initiated by raising intracellular calcium levels in the RBCs with the addition of CaCl2 and A23187 (a calcium ionophore) to final concentrations of 2 mM and 5 μM, respectively. After 10 minutes of incubation at room temperature, the RBCs are pelleted in a microcentrifuge, and the supernatant is removed and counted in a Wallac MicroBeta liquid scintillation counter.

Storage & Handling

• Storage: 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

KcsA, inhibit, Inhibitor, Gardos channel, ICA-17043, ICA17043, ICA 17043, PotassiumChannel, Potassium Channel, Senicapoc

Compound Identifiers

PubChem CID

216327