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ML-297

ML297, VU0456810, 1-(3,4-difluorophenyl)-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl) urea
A Potent and Selective Activator of GIRK1/2 Channels
Cat #: M-215
Alternative Name ML297, VU0456810, 1-(3,4-difluorophenyl)-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl) urea
  • Bioassay Tested
  • Source Synthetic
    MW: 328.32
    Purity: >99% (HPLC)
    Effective concentration 0.1-10 µM
    Structure
    Chemical name 1-(3,4-difluorophenyl)-3-(5-methyl-2-phenylpyrazol-3-yl)urea
    Molecular formula C17H14F2N4O
    CAS No.: 1443246-62-5
    PubChem CID 56642816
    Activity ML-297 is a potent and selective activator of GIRK1/2 channels (EC50=160-233 nM)1,2. ML-297 is selective for GIRK1/2 over GIRK1/3 and GIRK1/4 heteromers (with EC50 of 914 nM and 887 nM, respectively), and inactive on non-GIRK1-containing channels1-2. Active in vivo3.
    References-Activity
    1. Wen, W. et al. (2013) Bioorg. Med. Chem. Lett. 23, 4562.
    2. Lüscher, C. and Slesinger, P.A. (2010) Nat. Rev. Neurosci. 11, 301.
    3. Kaufmann, K. et al. (2013) ACS Chem. Neurosci. 4, 1278.
    Shipping and storage Store at -20°C.
    Solubility Soluble in DMSO. It is recommended to prepare a ≤10 mM stock in fresh DMSO prior to dilution in an aqueous solution. Centrifuge all products before handling (10000 x g 5 min).
    Storage of solutions Store at -20°C for several months. It is recommended to aliquot stock solutions to prevent repeated thawing and freezing.
    Our bioassay
    • Alomone Labs ML-297 activates heteromeric GIRK1/2 channels expressed in Xenopus oocytes.
      Alomone Labs ML-297 activates heteromeric GIRK1/2 channels expressed in Xenopus oocytes.
      Representative time course of GIRK1/2 (Kir3.1/Kir3.2) currents, measured at a holding potential of -80 mV in continuously applied high K+-containing bath solution (top dotted line), and significantly activated by 10 µM ML-297 (#M-215), as indicated.
    References - Scientific background
    1. Wen, W. et al. (2013) Bioorg. Med. Chem. Lett. 23, 4562.
    2. Lüscher, C. and Slesinger, P.A. (2010) Nat. Rev. Neurosci. 11, 301.
    3. Rifkin, R.A. et al. (2019) Trends Pharmacol. Sci. 38, 378.
    Scientific background

    ML-297 is a potent activator of GIRK channels; it shows a preference for the GIRK1/GIRK2 subunit combination compared to GIRK1/GIRK4 and is inactive on GIRK2/GIRK3 and a number of other potassium channels. ML297 is a useful tool to selectively probe GIRK1/2 channels function in vitro and in vivo. These properties make ML-297 the first and only molecule of its type to selectively probe GIRK1-containing GIRKs and hence it enables the studying of the role of GIRK1-containing GIRKs in numerous normal and pathophysiological conditions1.

    G protein-gated inwardly rectifying potassium (GIRK) channels hyperpolarize neurons in response to the activation of many G-protein coupled receptors. They are members of the large super-family of inwardly rectifying K+ channels (Kir), in which the inward current is significantly greater than the outward current. Their specific biochemical properties generate a slow inhibitory postsynaptic current that provides a sustained form of inhibition of neuronal activity2.

    GIRK channel activity has an important role in physiological responses, including pain perception and memory modulation. Moreover, abnormal GIRK function is implicated in altering neuronal excitability and cell death that may be important in the pathophysiology of human diseases such as epilepsy, Down’s syndrome, Parkinson’s disease and drug addiction. GIRK channels may therefore prove to be valuable new therapeutic targets for treating these health problems2.

    GIRK1-GIRK2 heterotetramers are believed to be the predominant form of GIRK channels expressed in brain3.

    Target GIRK1/2, GIRK1-containing GIRK channels
    Last update: 23/08/2020

    ML-297 (#M-215) is a highly pure, synthetic, and biologically active compound.

    For research purposes only, not for human use
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