| A blood-brain barrier-permeable, non-toxic phenyl-pyrazolylurea compound that acts as a direct, potent, fast, and reversible activator of GIRK1 (G-protein activated inward-rectifying K+ channel containing subunit 1) containing channels (EC50 = 162, 914, and 887nM in Thallium influx assay for GIRK1/2, GIRK1/3, and GIRK1/4 expressed in HEK-293 cell lines). Its action does not require the presence of an activated Gi GPCR. Shown to be inactive towards GIRK2, GIRK2/3, Kir2.1, KV7.4 and GABAA, and weakly active against a panel of 61 other receptors, ion channels, enzymes, transporters, and proteins even at higher concentration (~10uM). Exhibits desirable pharmacokinetic properties with good solubility (17.5uM), predicted hepatic clearance (88 ml/min/kg), and Tmax of 640nM and 130nM in plasma and brain, respectively. Shown to reduce locomotor function and seizure frequency in electroshock- and chemically-induced murine epilepsy models (60mg/kg, i.p). Synonyms: CID 56642816, VU0456810, 1-(3,4-Difluorophenyl)-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)urea, N-(3,4-Difluorophenyl)-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)urea CAS No: 1443246-62-5 Molecular Formula: C17H14F2N4O Solubility: DMSO Primary Target: GIRK1/Kir3.1-containing tetrameric GIRK channels Purity: 98% (HPLC) Appearance: White powder. Storage and Stability: May be stored at 4C. For long-term storage, aliquot and store at 4C. Do not freeze. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer. |
