1. PI3K/Akt/mTOR Stem Cell/Wnt Autophagy
  2. Organoid GSK-3 Wnt β-catenin Autophagy
  3. Laduviglusib

CHIR-99021  (Synonyms: Laduviglusib; CT99021; ラドゥビグルシブ)

製品番号: HY-10182 純度: 99.46%
COA 取扱説明書 Technical Support

Laduviglusib (CHIR-99021) is a potent, selective and orally active GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib enhances mouse and human embryonic stem cells self-renewal. Laduviglusib induces autophagy.

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CAS 番号 : 252917-06-9

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カスタマーレビュー

Based on 295 publication(s) in Google Scholar

Other Forms of Laduviglusib:

Top Publications Citing Use of Products

顧客検証

IF
Bio/Physico-chemical Assay
WB
In Vivo Efficacy Study
RT-PCR
Histological Imaging/Staining
Cell Proliferation/Viability Assay

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Feb 25;16(1):1774.  [Abstract]

    Viable cell numbers and PUFA-PC ratio after treatment with LY294002 (iPI3K, 10 µM), picropodophyllin (iRTK, 10 µM), ipatasertib (iAkt, 10 µM), or fatostatin (iSREBP1, 20 µM) for 48 h.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Mol Cell Proteomics. 2025 May 12:100991.  [Abstract]

    Laduviglusib monohydrochloride (18 mg/kg; i.p.; every other day) significantly reduced the phosphorylation level of GSK3α in CCl4-induced hepatic fibrosis mice.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Mol Cell Proteomics. 2025 May 12:100991.  [Abstract]

    Western blotting assay of collagen I expression in CCl4-induced hepatic fibrosis mice after treatment with GSK3α inhibitor Laduviglusib monohydrochloride (6-18 mg/kg; i.p.; every other day).

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Mol Cell Proteomics. 2025 May 12:100991.  [Abstract]

    GSK3α inhibitor Laduviglusib monohydrochloride (100 nM) significantly inhibited TGF-β-induced activation of HSCs and reduced COL1A1 production.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Mol Cell Proteomics. 2025 May 12:100991.  [Abstract]

    GSK3α inhibitor Laduviglusib monohydrochloride (100 nM) diminished the expression levels of both αSMA and COL1A1 in mouse primary HSCs and LX-2 cell line.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Mol Cell Proteomics. 2025 May 12:100991.  [Abstract]

    Liver tissues from vehicle- or Laduviglusib monohydrochloride (6-18 mg/kg; i.p.; every other day) -treated fibrotic mice were stained with H&E, Sirius Red, and α-SMA, and quantitative results of Sirius Red and α-SMA staining were shown.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Nat Genet. 2024 Feb;56(2):294-305.  [Abstract]

    Trophoblast organoids constructed from hTSCs-BL. Trophoblast markers: CDH1 and hCG. Briefly, hTSCs were cultured in hTSCs medium (DMEM/F12 supplemented with 0.1 mM 2-mercaptoethanol, 0.2% FBS, 0.5% Penicillin–Streptomycin, 0.3% BSA, 1% ITS-X supplement, 1.5 μg/ml L-ascorbicacid, 50 ng/mL Epidermal Growth Factor (EGF)(MedChemExpress), 2 μM CHIR99021 (MedChemExpress), 0.5 μM A83-01 (MedChemExpress), 1 μM SB431542 (MedChemExpress), 0.8 mM Valproic acid and 5 μM Y27632 (MedChemExpress).

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Nov;45(11):2290-2299.

    Schemes of generating Fsp1-Cre:R26R-loxp-tdTomato mice and drug treatment to induce in situ transdifferentiation. Fsp1-Cre mice were crossed with R26Rloxp-tdTomato mice in which the expression of tdTomato is prevented by a loxP-flanked STOP cassette. The F1 mice would have the red fluorescent protein tdTomato expressed specifically in the fibroblasts. CRFVPTM were given once a week for 6 weeks. Immunofluorescence staining of the cryosections of the hearts from Fsp1-Cre:R26R-loxp-tdTomato mice treated with vehicle (b) or CRFVPTM (c) for 6 weeks. C: CHIR99021, 14 mg/kg; R: RepSox, 8.6 mg/kg; F: Forskolin, 61.6 mg/kg; V: VPA, 250 mg/kg; T: TTNPB, 1 mg/kg and M: Rolipram, 2.5 mg/kg; P: Parnate, 2.7 mg/kg, CRFTM by oral gavage and VP by intraperitoneal injection once a week for 6 weeks in mice at about 8 weeks of age.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Nov;45(11):2290-2299.

    Whole-heart imaging with light-sheet fluorescence microscopy after tissue clearing of the hearts from Fsp1-Cre:R26R-loxp-tdTomato mice treated with vehicle (a) or CRFVPTM (b). (C: CHIR99021, 14 mg/kg; R: RepSox, 8.6 mg/kg; F: Forskolin, 61.6 mg/kg; V: VPA, 250 mg/kg; T: TTNPB, 1 mg/kg and M: Rolipram, 2.5 mg/kg; P: Parnate, 2.7 mg/kg, CRFTM by oral gavage and VP by intraperitoneal injection once a week for 6 weeks in mice at about 8 weeks of age).

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Nov;45(11):2290-2299.

    a Schemes of obtaining PDGFRα-DreER:R26R-rox-tdTomato mice and drug treatment to induce in situ cardiac reprogramming in PDGFRα-DreER:R26R-roxtdTomato mice. PDGFRα-DreER mice were mated with R26R-rox-tdTomato mice in which the expression of tdTomato is prevented by a roxflanked STOP cassette. The expression of tdTomato in fibroblasts was turned on by tamoxifen treatment. CRFVPTM were given once a week for 6 weeks. b Body weigh change of the mice after chemical treatment. Immunofluorescence staining of the cryosections of the hearts from PDGFRα-DreER:R26R-rox-tdTomato mice treated with vehicle (c) or CRFVPTM (d) for 6 weeks. (C: CHIR99021, 14 mg/kg; R: RepSox, 8.6 mg/kg; F: Forskolin, 61.6 mg/kg; V: VPA, 250 mg/kg; T: TTNPB, 1 mg/kg and M: Rolipram, 2.5 mg/kg; P: Parnate, 2.7 mg/kg, CRFTM by oral gavage and VP by intraperitoneal injection once a week for 6 weeks in mice at about 8 weeks of age).

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2024 Nov;45(11):2290-2299.

    Immunofluorescence staining of α-actinin in cryosections of hearts from Fsp1-Cre:R26R-loxp-tdTomato mice treated with 7 C cocktail (CRFVPTM) or cocktails by removing 1 compound from 7 C (7C-X) for 6 weeks in vivo with Fsp1-Cre:R26R-loxp-tdTomato mice. (C: CHIR99021, 14 mg/kg; R: RepSox, 8.6 mg/kg; F: Forskolin, 61.6 mg/kg; V: VPA, 250 mg/kg; T: TTNPB, 1 mg/kg and M: Rolipram, 2.5 mg/kg; P: Parnate, 2.7 mg/kg, CRFTM by oral gavage and VP by intraperitoneal injection once a week for 6 weeks in mice at about 8 weeks of age).

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2020 Apr 2;524(2):280-287.  [Abstract]

    Western blot analysis of Tcf7l1 protein levels in mESCs pre-treated with the indicative different small molecules for 1 h and then treated with CHIR for 24 h.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2020 Apr 2;524(2):280-287.  [Abstract]

    Western blot analysis of Tcf7l1 protein levels in mESCs pre-treated with D4476 or DMAT and then treated with CHIR or PD03 for 24 h.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Chemosphere. 2019 Feb:216:372-378.  [Abstract]

    AhR mediates EOM-inhibited cardiac differentiation by downregulating β-catenin expression in P19 cells. mRNA expression changes of β-catenin by Q-PCR. The concentrations of CH (CH223191, AhR antagonist) and CHIR (CHIR99021, Wnt activator) are 0.25 and 0.5 μM respectively.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Chemosphere. 2019 Feb:216:372-378.  [Abstract]

    AhR mediates EOM-inhibited cardiac differentiation by downregulating β-catenin expression in P19 cells. Percentage of cTnT positive cells at differentiation day 14. The concentrations of CH (CH223191, AhR antagonist) and CHIR (CHIR99021, Wnt activator) are 0.25 and 0.5 μM respectively.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Chemosphere. 2019 Feb:216:372-378.  [Abstract]

    AhR mediates EOM-inhibited cardiac differentiation by downregulating β-catenin expression in P19 cells. Percentage of cTnT positive cells at differentiation day 14. The concentrations of CH (CH223191, AhR antagonist) and CHIR (CHIR99021, Wnt activator) are 0.25 and 0.5 μM respectively.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Chemosphere. 2019 Feb:216:372-378.  [Abstract]

    AhR mediates EOM-inhibited cardiac differentiation by downregulating β-catenin expression in P19 cells. mRNA expression changes of β-catenin by Q-PCR. The concentrations of CH (CH223191, AhR antagonist) and CHIR (CHIR99021, Wnt activator) are 0.25 and 0.5 μM respectively.

    Laduviglusib purchased from MedChemExpress. Usage Cited in: Toxicology. 2016 Apr 29:355-356:31-8.  [Abstract]

    Western analysis of β-catenin protein level in zebrafish embryos exposed to EOM in the presence or absence of CH/CHIR (n = 3). Different letters indicate significant differences. Moreover, both CH and CHIR attenuate the EOM-induced changes in the protein level of b-catenin and in EROD activity.

    GSK-3 アイソフォーム固有の製品をすべて表示:

    Wnt アイソフォーム固有の製品をすべて表示:

    • 生物活性

    • 純度とドキュメンテーション

    • 参考文献

    • カスタマーレビュー

    製品説明

    Laduviglusib (CHIR-99021) is a potent, selective and orally active GSK-3α/β inhibitor with IC50s of 10 nM and 6.7 nM. Laduviglusib shows >500-fold selectivity for GSK-3 over CDC2, ERK2 and other protein kinases. Laduviglusib is also a potent Wnt/β-catenin signaling pathway activator. Laduviglusib enhances mouse and human embryonic stem cells self-renewal. Laduviglusib induces autophagy[1][2][3].

    IC50 & Target[1]

    GSK-3β

    6.7 nM (IC50)

    GSK-3α

    10 nM (IC50)

    cdc2

    8800 nM (IC50)

    Cellular Effect
    Cell Line Type Value Description References
    CHO EC50
    0.13 μM
    Compound: 1
    Inhibition of GSK3 in CHO cells expressing insulin receptor assessed as activation of glycogen synthase measured after 30 mins in presence of glucose-6-phosphate by filter paper assay
    Inhibition of GSK3 in CHO cells expressing insulin receptor assessed as activation of glycogen synthase measured after 30 mins in presence of glucose-6-phosphate by filter paper assay
    [PMID: 31926786]
    HepG2 EC50
    1.5 μM
    Compound: 1, CHIR-99021
    Inhibition of GSK3-beta in human HepG2 cells assessed as incorporation of [3H]glucose into glycogen after 3 hrs by liquid scintillation counting
    Inhibition of GSK3-beta in human HepG2 cells assessed as incorporation of [3H]glucose into glycogen after 3 hrs by liquid scintillation counting
    [PMID: 22261023]
    体外実験

    Laduviglusib (1-10 μM, 3 days) reduces the viability of the ES-D3 cells with an IC50 of 4.9 μM[2].
    Laduviglusib (5 μM, 48 h) activates the canonical Wnt-pathway in ES-D3 cells and ES-CCE cells[2].
    Laduviglusib (3 μM, 4 days) inhibits ES cell differentiation into neural cells[3].
    Laduviglusib (1 μM, 2 weeks) inhibits adipogenesis by blocking induction of C/EBPα and PPARγ in 3T3-L1 preadipocytes[4].
    Laduviglusib (2.5 μM, 24 h) protects Lgr5+ cells against radiation-induced apoptosis[5].

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

    Cell Viability Assay[2]

    Cell Line: ES-D3 cells
    Concentration: 1-10 μM
    Incubation Time: 3 days
    Result: Reduced the viability of the ES-D3 cells by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM
    体内実験

    Laduviglusib (30 mg/kg, p.o ) rapidly lowers plasma glucose[1].
    Laduviglusib (2 mg/kg, i.p.) protects mice against radiation-induced lethal GI injury[5].

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

    Animal Model: ZDF rats[1]
    Dosage: 30 mg/kg
    Administration: Oral administration
    Result: Lowered plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration.
    Animal Model: WT C57BL/6 mice[5]
    Dosage: 2 mg/kg
    Administration: Intraperitoneal injection (i.p.)
    Result: Blocked crypt apoptosis and increased Lgr5+ cell survival.
    分子量

    465.34

    分子式

    C22H18Cl2N8

    CAS 番号
    Appearance

    Solid

    Color

    Off-white to light brown

    SMILES

    N#CC1=CC=C(N=C1)NCCNC2=NC=C(C(C3=CC=C(Cl)C=C3Cl)=N2)C4=NC=C(N4)C

    輸送条件

    Room temperature in continental US; may vary elsewhere.

    保管条件
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    溶剤 & 溶解度
    体外: 

    DMSO : 16.67 mg/mL (35.82 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.1490 mL 10.7448 mL 21.4897 mL
    5 mM 0.4298 mL 2.1490 mL 4.2979 mL
    10 mM 0.2149 mL 1.0745 mL 2.1490 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, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

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    一般には略語で表示されます:C1V1 = C2V2

    濃度 (開始)

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    体内:

    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    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.08 mg/mL (4.47 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

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

      Solubility: ≥ 2.08 mg/mL (4.47 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 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 (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    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:  0.5% CMC-Na/saline water

      Solubility: 5 mg/mL (10.74 mM); Suspended solution; Need ultrasonic

    • Protocol 2

      Add each solvent one by one:  20% SBE-β-CD in Saline adjusted to pH 4-4.5 with 1 N Acetic

      Solubility: 5 mg/mL (10.74 mM); Clear solution; Need ultrasonic

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

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    Please enter your animal formula composition:
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    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.
    純度とドキュメンテーション

    純度: 99.76%

    参考文献

    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, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.1490 mL 10.7448 mL 21.4897 mL 53.7242 mL
    5 mM 0.4298 mL 2.1490 mL 4.2979 mL 10.7448 mL
    10 mM 0.2149 mL 1.0745 mL 2.1490 mL 5.3724 mL
    15 mM 0.1433 mL 0.7163 mL 1.4326 mL 3.5816 mL
    20 mM 0.1074 mL 0.5372 mL 1.0745 mL 2.6862 mL
    25 mM 0.0860 mL 0.4298 mL 0.8596 mL 2.1490 mL
    30 mM 0.0716 mL 0.3582 mL 0.7163 mL 1.7908 mL
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    • Molarity Calculator

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    The dilution calculator equation

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

    一般には略語で表示されます:C1V1 = C2V2

    濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
    × = ×
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    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.

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    製品名:
    Laduviglusib
    製品番号:
    HY-10182
    数量:
    MCE 日本正規代理店: