2. Stem Cell/Wnt
  3. Porcupine
  4. LGK974

LGK974 (WNT974) is an orally bioavailable and specific Porcupine (PORCN) inhibitor with an IC50 of 0.1 nM.

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

LGK974 Chemical Structure

LGK974 Chemical Structure

CAS No. : 1243244-14-5

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Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 132 In-stock
Solution
10 mM * 1 mL in DMSO USD 132 In-stock
Solid
5 mg USD 120 In-stock
10 mg USD 204 In-stock
50 mg USD 720 In-stock
100 mg USD 1128 In-stock
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Customer Review

Based on 27 publication(s) in Google Scholar

LGK974 Related Antibodies

Top Publications Citing Use of Products

    LGK974 purchased from MedChemExpress. Usage Cited in: Cell Stem Cell. 2020 Sep 3;27(3):413-429.e4.  [Abstract]

    IF images of uninjured, 48 hpi, and 72 hpi mouse airway epithelia wild-type mice treated with vehicle or LGK974 assessing BrdU incorporation. Relative to vehicle-treated mice, LGK974-treated mice exhibited an attenuated SAE with few BrdU+ ABSCs, thereby phenocopying the repair response of K5-CreER;Ctnnb1fl/fl mouse tracheas.

    LGK974 purchased from MedChemExpress. Usage Cited in: Exp Cell Res. 2016 Jul 15;345(2):206-17.  [Abstract]

    Inhibition of PORCN abolishes Runx2 induction stimulated by β-GP. VSMCs are pretreated with LGK974 (1nM) for 30 min, then incubated with β-GP (10mM) for 24h, and the cell lysates are immunoblotted with antibodies against Runx2 and β-actin, respectively.

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    LGK974 (WNT974) is an orally bioavailable and specific Porcupine (PORCN) inhibitor with an IC50 of 0.1 nM[1].

    IC50 & Target

    Porcupine[1]
    In Vitro

    LGK974 effectively displaces [3H]-GNF-1331 with an IC50 of 1 nM in the PORCN radioligand binding assay. LGK974 potently reduces Wnt-dependent AXIN2 mRNA levels in HN30 cells with an IC50 of 0.3 nM[1].

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

    LGK974 Related Antibodies
    In Vivo

    LGK974, a drug that targets Porcupine, a Wnt-specific acyltransferase. LGK974 potently inhibits Wnt signaling, has strong efficacy in rodent tumor models, and is well-tolerated. Toxicology studies are performed on nontumor bearing rats at 3 and 20 mg/kg. At the efficacious dose of 3 mg/kg per day for 14 d, LGK974 is well-tolerated without abnormal histopathological findings in Wnt-dependent tissues, including the intestine, stomach, and skin. When rats are administrated a very high dose of 20 mg/kg per day for 14 d, loss of intestinal epithelium is observed, consistent with the concept that Wnt is required for intestinal tissue homeostasis[1].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Clinical Trial
    Molecular Weight

    396.44

    Formula

    C23H20N6O
    CAS No.
    Appearance

    Solid

    Color

    White to light brown

    SMILES

    O=C(NC1=NC=C(C2=NC=CN=C2)C=C1)CC3=CN=C(C4=CC(C)=NC=C4)C(C)=C3
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 32 mg/mL (80.72 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.5224 mL 12.6122 mL 25.2245 mL
    5 mM 0.5045 mL 2.5224 mL 5.0449 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

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

      Solubility: 2.5 mg/mL (6.31 mM); Suspended solution; Need ultrasonic and warming

      This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

      Solubility: ≥ 2.5 mg/mL (6.31 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.92%

    COA (245 KB) HNMR (258 KB) LCMS (95 KB) Elemental Analysis Report (103 KB)

    Handling Instructions (2659 KB)
    References
    Cell Assay
    [1]

    HN30 cells and UMSCC cells are used. For TaqMan assay, 2×106 cells per well are plated into six-well cell culture plates and treated with or without LGK974 in amultipoint dose-response. RNA samples are collected after 48 h. For colony formation assays, 2×103 cells per well are plated into six-well cell culture plates with or without compound treatment. Cells are stained with crystal violet 1 wk later[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Mice and Rats[1]
    Nude mice (or nude rats) bearing the mouse mammary tumor virus-Wnt1, HN30, or SNU1076 tumors are randomized according to tumor volume. LGK974 is formulated in 10% (vol/vol) citrate buffer (pH 2.8)/90% (vol/vol) citrate buffer (pH 3.0) or 0.5% MC/0.5% Tween 80 and administered by oral gavage at a dosing volume of 10 μL/g animal body weight. Body weight is monitored daily, and tumor sizes are assessed three times per week after the tumors are palpable. Tumor sizes are determined by using caliper measurements. Tumor volumes are calculated with a formula (length×width×height)/2. The plasma concentrations and exposures of LGK974 in the tumor-bearing nude mice (n=2 per dosing group) are determined on day 14. Blood samples (50 μL) are collected by serial retroorbital sampling at 1, 3, 7, 16, and 24 h postdose. The blood samples are centrifuged, and plasma is separated and frozen until analysis by liquid chromatography/MS/MS. For tolerability studies, LGK974 is administrated to nontumor-bearing Wistar rats one time per day by oral gavage at 3 or 20 mg/kg per day. Necropsies are performed at the end of the study. Tissues are fixed in 10% (vol/vol) neutralbuffered formalin, sectioned, and subjected to H&E staining.

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

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.5224 mL 12.6122 mL 25.2245 mL 63.0612 mL
    5 mM 0.5045 mL 2.5224 mL 5.0449 mL 12.6122 mL
    10 mM 0.2522 mL 1.2612 mL 2.5224 mL 6.3061 mL
    15 mM 0.1682 mL 0.8408 mL 1.6816 mL 4.2041 mL
    20 mM 0.1261 mL 0.6306 mL 1.2612 mL 3.1531 mL
    25 mM 0.1009 mL 0.5045 mL 1.0090 mL 2.5224 mL
    30 mM 0.0841 mL 0.4204 mL 0.8408 mL 2.1020 mL
    40 mM 0.0631 mL 0.3153 mL 0.6306 mL 1.5765 mL
    50 mM 0.0504 mL 0.2522 mL 0.5045 mL 1.2612 mL
    60 mM 0.0420 mL 0.2102 mL 0.4204 mL 1.0510 mL
    80 mM 0.0315 mL 0.1577 mL 0.3153 mL 0.7883 mL
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    LGK974 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    LGK9741243244-14-5WNT974LGK 974LGK-974WNT 974WNT-974PorcupineInhibitorinhibitorinhibit

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