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505820 | GIRK Activator, ML297 - CAS 1443246-62-5 - Calbiochem

505820
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      Overview

      Replacement Information

      Key Specifications Table

      Empirical FormulaCAS #
      C₁₇H₁₄F₂N₄O 1443246-62-5

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      5.05820.0001
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          Glass bottle 10 mg
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          Description
          OverviewA 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 887 nM 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 (~10 µM). Exhibits desirable pharmacokinetic properties with good solubility (17.5 µM), predicted hepatic clearance (88 ml/min/kg), and Tmax of 640 nM and 130 nM in plasma and brain, respectively. Shown to reduce locomotor function and seizure frequency in electroshock- and chemically-induced murine epilepsy models (60 mg/kg, i.p).
          Catalogue Number505820
          Brand Family Calbiochem®
          Synonyms1-(3,4-Difluorophenyl)-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)urea, N-(3,4-Difluorophenyl)-Nʹ-(3-methyl-1-phenyl-1H-pyrazol-5-yl)urea, CID 56642816, VU0456810
          References
          ReferencesWen, W., et al. 2013. Bioorg. Med. Chem. Lett. 23, 4562.
          Kaufmann, K., et al. 2013. ACS Chem. Neurosci. 4, 1278.
          Product Information
          CAS number1443246-62-5
          FormWhite powder
          Hill FormulaC₁₇H₁₄F₂N₄O
          Chemical formulaC₁₇H₁₄F₂N₄O
          ReversibleY
          Structure formula Image
          Applications
          Biological Information
          Primary TargetGIRK1/Kir3.1-containing tetrameric GIRK channels
          Purity≥98% by HPLC
          Physicochemical Information
          Cell permeableY
          Dimensions
          Materials Information
          Toxicological Information
          Safety Information according to GHS
          Safety Information
          Product Usage Statements
          Storage and Shipping Information
          Ship Code Ambient Temperature Only
          Toxicity Standard Handling
          Storage +2°C to +8°C
          Protect from Light Protect from light
          Do not freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Packaging Information
          Packaged under inert gas Packaged under inert gas
          Transport Information
          Supplemental Information
          Specifications

          Documentation

          References

          Reference overview
          Wen, W., et al. 2013. Bioorg. Med. Chem. Lett. 23, 4562.
          Kaufmann, K., et al. 2013. ACS Chem. Neurosci. 4, 1278.
          Data Sheet

          Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

          Revision18-October-2013 JSW
          Synonyms1-(3,4-Difluorophenyl)-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)urea, N-(3,4-Difluorophenyl)-Nʹ-(3-methyl-1-phenyl-1H-pyrazol-5-yl)urea, CID 56642816, VU0456810
          DescriptionA cell-permeable phenyl-pyrazolylurea that directly activates GIRK1/Kir3.1-containing tetrameric GIRK channels (EC50 = 162, 887 and 914 nM, respectively, in Thallium flux assays using GIRK1-2, GIRK1-4, or GIRK1-3 HEK-293 transfectants; EC50 = 584 and 1,400 nM, respectively, in whole-cell voltage clamp measurements using GIRK1-2 or GIRK1-4 HEK-293 transfectants) in a GPCR-independent manner, while being ineffective toward Kir2.1, KV7.4, or GIRK channels composed of GIRK2-3 (Kir3.2-Kir3.3) or GIRK2 alone. Selectivity studies against 67 receptors reveal only weak antagonistic activity against hERG (IC50 = 10 µM; Inhmax/ICmax = 59.6%/100 µM), rat GABAA (muscimol), human Sigma δ1, and human 5-HT2B receptors (49%, 49%, and 46% inhibition, respectively, at 10 µM). Despite its suboptimal metabolic stability and brain permeability in mice (Cmax/Tmaxmax = 130 nM/30 min; 60 mg/kg i.p.), ML297 nevertheless is demonstrated to be at least 4.9-times more effective than Valproate (Cat. No. 676380) in prolonging the latency to seizure following lethal electric shock and in preventing GABAA antagonist PTZ-induced convulsion and death in two murine epilepsy models (60 mg/kg i.p.) in vivo.
          FormWhite powder
          Intert gas (Yes/No) Packaged under inert gas
          CAS number1443246-62-5
          Chemical formulaC₁₇H₁₄F₂N₄O
          Structure formula
          Purity≥98% by HPLC
          SolubilityDMSO (100 mg/ml). Use only fresh DMSO for reconstitution.
          Storage +2°C to +8°C
          Protect from light
          Do Not Freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Toxicity Standard Handling
          ReferencesWen, W., et al. 2013. Bioorg. Med. Chem. Lett. 23, 4562.
          Kaufmann, K., et al. 2013. ACS Chem. Neurosci. 4, 1278.