1. TGF-beta/Smad
    Autophagy
  2. TGF-β Receptor
    Autophagy

LY2109761 

Cat. No.: HY-12075 Purity: 99.95%
Handling Instructions

LY2109761 is an orally active, selective TGF-β receptor type I/II inhibitor with Kis of 38 nM and 300 nM, respectively.

For research use only. We do not sell to patients.

LY2109761 Chemical Structure

LY2109761 Chemical Structure

CAS No. : 700874-71-1

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 119 In-stock
Estimated Time of Arrival: December 31
5 mg USD 108 In-stock
Estimated Time of Arrival: December 31
10 mg USD 180 In-stock
Estimated Time of Arrival: December 31
50 mg USD 540 In-stock
Estimated Time of Arrival: December 31
100 mg USD 828 In-stock
Estimated Time of Arrival: December 31
200 mg USD 1188 In-stock
Estimated Time of Arrival: December 31
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Customer Review

    LY2109761 purchased from MCE. Usage Cited in: Int J Mol Med. 2015 Jun;35(6):1667-74.

    Inhibition of the TGF-β1/Smad2 pathway decreases H2O2-induced human umbilical vein endothelial cell (HUVEC) apoptosis, but not oxidative stress. Western blot analysis is performed to determine protein expression in the HUVECs in the control, model, AST Ⅳ and LY2109761 groups.

    LY2109761 purchased from MCE. Usage Cited in: J Hepatol. 2015 Oct;63(4):863-73.

    Blocking the TGF-beta and ERK signalling effectively inhibits EDIL3 mediated angiogenesis and invasion. Western blotting analysis of the expression of p-ERK and p-Smad2 in DMSO- and VX-11e or LY2109761-treated HuH7-p-lenti-EDIL3 cells. GAPDH is used as a loading control.

    LY2109761 purchased from MCE. Usage Cited in: Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836.

    NRK-49F cells are treated with TGF-β1 for the indicated time. The levels of p-STAT3, p-AKT, p-GSK3α, and p-GSK3β expression are detected in comparison with the levels of total STAT3, AKT, GSK3α, GSK3β, and with GAPDH as the loading control.

    LY2109761 purchased from MCE. Usage Cited in: Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836.

    LY2109761 at 100 nM, 10 μM, or 50 μM is added for 30 min to block TGFβR1/2 prior to TGF-β1-treatment, then proteins are collected, and the levels of Sphk2, fibronectin, and α-SMA are detected by Western blotting.

    LY2109761 purchased from MCE. Usage Cited in: Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836.

    NRK-49F cells are preincubated with 100 nM, 10 μM, or 50 μM Smad3 inhibitor SIS3 for 30 min followed by TGF-β1 (2 ng/mL) stimulation for 12 h. Then, the expression of Sphk2, fibronectin, and α-SMA is determined by Western blotting.

    LY2109761 purchased from MCE. Usage Cited in: Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836.

    NRK-49F cells are pretreated with Fyn inhibitor SU6656 (1 μM) for 30 min, followed by TGF-β1 stimulation for 12 h, and then protein levels of fibronectin and α-SMA are determined by Western blotting.

    LY2109761 purchased from MCE. Usage Cited in: Mol Immunol. 2018 Oct 2;103:173-181.

    TRPM7 mRNA and protein expressions are effectively suppressed by LY2109761 and SIS3 in ASMCs compared with those in 10 ng/mL TGF-β1-stimulated cells.

    LY2109761 purchased from MCE. Usage Cited in: Cell Biol Int. 2017 Sep;41(9):960-968.

    The phosphorylation level of Smad2 is significantly inhibited by LY2109761. The M2 macrophage-induced increase of α-SMA and decrease of E-cadherin and CK-18 are inhibited by LY2109761.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    LY2109761 is an orally active, selective TGF-β receptor type I/II inhibitor with Kis of 38 nM and 300 nM, respectively.

    IC50 & Target

    Ki: 38 nM (TβRI), 300 nM (TβRII)

    In Vitro

    LY2109761 significantly inhibits the growth of L3.6pl/GLT soft agar colonies in a dose-dependent manner, and results in appr 33% inhibition at 2 μM and 73% inhibition at 20 μM. Targeting TβRI/II kinase activity with LY2109761 (5 μM) almost completely suppresses both the basal and TGF-β1-stimulated migration of L3.6pl/GLT cells[1]. LY2109761 induces a dose-dependent reduction in phosphorylation of Smad-2. HLE endogenous phosphorylation of Smad-2 is inhibited by LY2109761. LY2109761 blocks migration on different ECM proteins and invasion of both HLE and HLF through a 3-dimensional structure. LY2109761 increases E-cadherin mRNA expression after 24 hours and protein levels after 48 hours[2]. LY2109761 pretreatment reduces clonogenic survival in cell cultures of U87MG and T98 following radiation, resulting in an increase in the radiosensitivity with a DEF0.1 of 1.30 and 1.37, respectively[3].

    In Vivo

    LY2109761 (50 mg/kg, p.o.) greatly reduces the tumor volume and increases the median survival duration of the mice to 45.0 days. The mice treated with LY2109761 develop significantly fewer metastatic lesions and, in some of them, no metastatic lesion, as indicated by the GFP signal, can be identified in the abdomen[1]. LY2109761 enhances radiation-induced tumor growth delay in a U87MG subcutaneous xenograft tumor model in BALB/c nude mice. LY2109761 increases survival in an orthotopical CSLC glioblastoma model and enhanced antitumor activity of radiation[2].

    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 30 mg/mL (67.95 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.2649 mL 11.3245 mL 22.6490 mL
    5 mM 0.4530 mL 2.2649 mL 4.5298 mL
    10 mM 0.2265 mL 1.1325 mL 2.2649 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.08 mg/mL (4.71 mM); Clear solution

    References
    Cell Assay
    [1]

    L3.6pl/GLT cells are washed twice with cold PBS and lysed at 4°C into RIPA buffer (50 mM Tris HCl [pH 8], 150 mM NaCl, 1% NP-40, 0.5% sodium deoxycolate, and 0.1% SDS). Tumor and liver specimens are homogenized into RIPA buffer with an electric homogenizer and then maintained in constant agitation for two hours at 4°C. The lysates are cleared by centrifugation. Each lysate (20 µg of protein) is separated by 8% SDS-PAGE and probed with polyclonal rabbit antibodies against total ERK1/2, TβRI, and TβRII or with monoclonal mouse antibodies against phosphorylated Smad2, total Smad2, phosphorylated ERK1/2, and phosphorylated and total JNK. Immunoreactive proteins are visualized with Lumi-Light Western blotting substrate according to the manufacturer's instructions. phosphorylated Smad2/Smad2 band density ratios are calculated using the ImageQuant software.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Fifty mice are randomLy allocated into five groups (n=5 mice per group) to receive p.o. vehicle for 50 μL of LY2109761 or 50 mg/kg LY2109761 twice a day p.o. On day 0, mice are anesthetized with 1.5% isofluorane-air mixture, a small left abdominal flank incision is created, and the spleen is carefully exteriorized. L3.6pl/GLT or C5LM2/GLT cells (1.0×105 cells/50 μL of HBSS), cultured in the presence of LY2109761 (5 μM) or DMSO from day −5 to day 0, are inoculated into the spleen with a 30-gauge needle. A visible paling of the spleen is the criterion for successful inoculation. After 10 min, the spleen is removed using a high-temperature cautery to avoid the possibility that the ectopic growth of pancreatic tumor cells in the spleen could be a confounding source of hematogenous liver metastatic cells. The abdominal wall is closed in one layer with wound clips. Treatment with 50 mg/kg LY2109761 twice a day p.o. (days 1-5 of each week after inoculation) is continued for one group of untreated mice inoculated with untreated cells.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    441.52

    Formula

    C₂₆H₂₇N₅O₂

    CAS No.

    700874-71-1

    SMILES

    N12N=C(C(C3=C4C=CC(OCCN5CCOCC5)=CC4=NC=C3)=C1CCC2)C6=NC=CC=C6

    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

    Purity: 99.95%

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    Product Name:
    LY2109761
    Cat. No.:
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    Cat. No.: HY-12075