1. TGF-beta/Smad
  2. TGF-β Receptor

LY-364947 (Synonyms: HTS466284)

Cat. No.: HY-13462 Purity: 98.91%
Handling Instructions

LY-364947 is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM, and exhibits 7-fold selectivity over TGFβR-II.

For research use only. We do not sell to patients.
LY-364947 Chemical Structure

LY-364947 Chemical Structure

CAS No. : 396129-53-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 98 In-stock
5 mg USD 89 In-stock
10 mg USD 118 In-stock
50 mg USD 358 In-stock
100 mg   Get quote  
200 mg   Get quote  

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    LY-364947 purchased from MCE. Usage Cited in: World J Gastroenterol. 2017 Apr 7;23(13):2330-2336.

    Notch γ-secretase inhibitor attenuates notch and transforming growth factor-β signaling pathways in peripheral blood mononuclear cells of liver fibrosis rats. Western blot analysis of protein expression of Notch1, Hes1, Hes5, TGF-β and Smad3 and quantification in PBMCs (2 × 106) from rats treated with DAPT or DMSO for 24 h.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    LY-364947 is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM, and exhibits 7-fold selectivity over TGFβR-II.

    IC50 & Target

    IC50: 59 nM (TGFβR-I)

    In Vitro

    LY-364947 is an ATP competitive and tight-binding inhibitor, inhibiting phosphorylation of P-Smad3 by TGFβR-I Kinase with Ki of 28 nM. LY-364947 inhibits in vivo Smad2 phosphorylation within the NMuMg cells with IC50 of 135 nM. LY-364947 reverses TGF-β-mediated growth inhibition in NMuMg cells with IC50 of 0.218 μM. LY-364947 potentiates the xVent2-lux BMP4 response in NMuMg cells by 30% at concentrations as low as 0.25 μM. LY-364947 (2 μM) prevents TGF-β-induced epithelial−mesenchymal transition in NMuMg cells[1]. LY-364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours[2]. LY-364947 promotes nuclear export of Foxo3a, with low Smad2/3 and high Akt phosphorylation levels in leukaemia-initiating cells. LY-364947 (< 20 μM) suppresses leukaemia-initiating cells colony-forming ability after co-culture with OP-9 stromal cells[3].

    In Vivo

    LY-364947 (1 mg/kg, i.p.) accelerates lymphangiogenesis, as evidence by significantly increasing the LYVE-1-positive areas in a mouse model of chronic peritonitis. LY-364947 (1 mg/kg, i.p.) significantly increases the LYVE-1-positive areas in tumor tissues in tumor xenograft models using BxPC3 pancreatic adenocarcinoma cells[2]. LY-364947 (25 mg/kg) increases p-Akt and decreases nuclear Foxo3a in leukaemia-initiating cells in CML-affected mice[3]

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 3.6724 mL 18.3621 mL 36.7242 mL
    5 mM 0.7345 mL 3.6724 mL 7.3448 mL
    10 mM 0.3672 mL 1.8362 mL 3.6724 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    The IC50 of LY-364947 at different enzyme concentrations are determined by the filter-binding assay. Typically, 40 μL reactions in 50 mM HEPES at pH 7.5, 1 mM NaF, 200 μM pKSmad3(-3), and 50 mM ATP containing a titration of each inhibitor with concentrations of 1600, 800, 400, 200, 100, 50, 25, and 0 nM are incubated at 30°C for 30 min. The IC50 is calculated using a nonlinear regression method with GraphPad Prism software. The binding type is determined by plotting the correlation between enzyme concentrations and IC50 values. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    LY-364947 is dissolved in 5 mg/mL in DMSO.

    BALB/c nude mice 5 to 6 weeks of age are used in the assay. Parental, or VEGF-C- or TGF-β1-expressing tumor cells (5×106) in 100 μL PBS are implanted subcutaneously into male nude mice and allowed to grow for 2 to 3 weeks to reach proliferative phase, before initiation of TβR-I inhibitor administration. TβR-I inhibitor LY-364947, dissolved in 5 mg/mL in DMSO and diluted with 100 μL PBS, or the vehicle control, is injected intraperitoneally at 1 mg/kg, 3 times a week for 3 weeks. Excised samples are directly frozen in dry-iced acetone for immunohistochemistry. Frozen samples are further sectioned at 10-μm thickness in a cryostat and subsequently incubated with primary and secondary antibodies. Samples are observed using a confocal microscope. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    272.3

    Formula

    C₁₇H₁₂N₄

    CAS No.

    396129-53-6

    SMILES

    C1(C2=CNN=C2C3=NC=CC=C3)=CC=NC4=CC=CC=C14

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: 25 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Inquiry Information

    Product Name:
    LY-364947
    Cat. No.:
    HY-13462
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