ARN23746 is a potent and selective inhibitor of the Na⁺-K⁺-2Cl⁻ cotransporter 1 (NKCC1), a key regulator of intracellular chloride homeostasis and neuronal excitability. In biochemical assays, ARN23746 inhibits human NKCC1 with an IC₅₀ of approximately 2.1 µM, showing over 30-fold selectivity against NKCC2. In preclinical models, it effectively modulates GABAergic signaling by reducing intracellular Cl⁻ levels, thereby enhancing the inhibitory action of GABA. In vivo, ARN23746 crosses the blood–brain barrier and exhibits antiepileptic activity in rodent seizure models without affecting renal NKCC2-mediated function, suggesting a favorable therapeutic window for central nervous system disorders such as epilepsy or neurodevelopmental diseases involving altered chloride homeostasis.
MedKoo Cat#: 464855
Name: ARN23746
CAS#: 2497525-96-7
Chemical Formula: C17H25F3N2O4S
Exact Mass: 410.1487
Molecular Weight: 410.45
Elemental Analysis: C, 49.75; H, 6.14; F, 13.89; N, 6.83; O, 15.59; S, 7.81
The following data is based on the product molecular weight 410.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
