2. Stem Cell/Wnt
  3. Smo
  4. Sonidegib

Sonidegib  (Synonyms: Erismodegib; LDE225; NVP-LDE225)

Cat. No.: HY-16582A Purity: 99.94%
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Sonidegib (Erismodegib) is a potent and selective Smo antagonist with IC50 of 1.3 nM and 2.5 nM for mouse and human Smo in binding assay, respectively.

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

Sonidegib Chemical Structure

Sonidegib Chemical Structure

CAS No. : 956697-53-3

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
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 USD 73 In-stock
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10 mM * 1 mL in DMSO USD 73 In-stock
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10 mg USD 92 In-stock
50 mg USD 198 In-stock
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Based on 6 publication(s) in Google Scholar

Other Forms of Sonidegib:

Sonidegib Related Antibodies

Top Publications Citing Use of Products

    Sonidegib purchased from MedChemExpress. Usage Cited in: J Genet Genomics. 2018 May 20;45(5):237-246.  [Abstract]

    Drug-feeding scheme (upper panel). Memory rescuing effects through treatment with LDE225 (LDE) or Vismodegib (VIS) at 20 mg/kg for 7.5-m-old and 15-m-old mice (lower panel, n=7 for each group).

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Sonidegib (Erismodegib) is a potent and selective Smo antagonist with IC50 of 1.3 nM and 2.5 nM for mouse and human Smo in binding assay, respectively[1].

    IC50 & Target

    IC50: 1.3 nM (mSmo), 2.5 nM (hSmo)[1]
    In Vitro

    The IC50 values for Sonidegib (NVP-LDE225) for the major human CYP450 drug metabolizing enzymes is greater than 10 μM[1]. Sonidegib (LDE225), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with Nilotinib, inhibits the Hh pathway in CD34+ chronic phase (CP)-chronic myeloid leukaemia (CML) cells, reducing the number and self-renewal capacity of CML leukaemia stem cell (LSC). Sonidegib interacts directly with SMO, in a similar fashion to cyclopamine, to reduce expression of downstream Hh signaling targets. Primary CD34+ CP-CML cells are cultured in serum free media (SFM)±Sonidegib for 6, 24 and 72 hours (h). At 72 h, while there is variability between the biological samples, GLI1 is significantly downregulated following exposure to Sonidegib (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01)[2].

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

    Sonidegib Related Antibodies
    In Vivo

    Sonidegib (NVP-LDE225) is a weak base with a measured pKa of 4.2 and exhibits relatively poor aqueous solubility. In the subcutaneous Ptch+/-p53-/- medulloblastoma allograft mouse model, Sonidegib demonstrates dose-related antitumor activity after 10 days of oral administration of a suspension of the diphosphate salt. At a dose of 5 mg/kg/day qd, Sonidegib significantly inhibits tumor growth, corresponding to a T/C value of 33% (p<0.05 as compared to vehicle controls). When dosed at 10 and 20 mg/kg/day qd, Sonidegib affords 51 and 83% regression, respectively[1]. Bone marrow cells and spleen cells from a subset of treated mice are transplanted into secondary recipient mice. Transplantation of either bone marrow (BM) or spleen cells from mice treated with Sonidegib (LDE225)+Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to Sonidegib or Nilotinib alone[2].

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

    485.50

    Formula

    C26H26F3N3O3
    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    SMILES

    O=C(C1=C(C)C(C(C=C2)=CC=C2OC(F)(F)F)=CC=C1)NC3=CC=C(N=C3)N4C[C@@H](C)O[C@@H](C)C4
    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 : 50 mg/mL (102.99 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 2.0597 mL 10.2987 mL 20.5973 mL
    5 mM 0.4119 mL 2.0597 mL 4.1195 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)

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

    V1

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    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    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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% (20% SBE-β-CD in Saline)

      Solubility: 2.5 mg/mL (5.15 mM); Suspended solution; Need ultrasonic

      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.

    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:  75% PEG300    25% (5% Dextrose in Water)

      Solubility: 2 mg/mL (4.12 mM); Clear solution; Need ultrasonic

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

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

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    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
    References
    Cell Assay
    [2]

    CD34+ CP-CML cells are seeded in SFM alone±Sonidegib±Nilotinib and cultured for 24-72 h prior to assessment. Proliferation is measured using colorimetric assessment of BrDU incorporation. Proportion of viable cells versus those in early and late apoptosis is assessed by flow cytometry using annexin V-FITC and 7-amino-actinomycin D (7-AAD, Via-Probe solution). Cell cycle status is assessed using Ki67 (FITC) expression and 7-AAD incorporation.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [2]

    Mice[2]
    The transgenic EGFP+/SCLtTA/TRE-BCR-ABL mouse model is used to investigate the effect of Sonidegib treatment on CML LSC in vivo. Scl-tTa-BCR-ABL mice in the FVB/N background are crossed with transgenic GFP-expressing mice. Bone marrow cells are obtained 4 weeks post induction, GFP+ cells are selected by flow cytometry and transplanted by tail vein injection (106 cells/mouse) into wild-type FVB/N recipient mice, irradiated at 900 cGy, generating a large cohort of mice with similar time of onset of leukemia. Blood samples obtained 4 weeks post transplantation confirmed a neutrophilic leukocytosis in recipient mice. Mice are treated with Nilotinib (50 mg/kg by gavage, daily), Sonidegib (80 mg/kg by gavage, daily), Sonidegib+Nilotinib, or with vehicle alone (control). After 3 weeks of treatment, animals are euthanised and marrow content of femurs and tibiae, spleen cells and blood obtained. Total white cell count (WCC), GFP-expressing WCC, myeloid cells, and GFP+ progenitors and stem cells are measured by flow cytometry. Survival is assessed in a subset of mice for 120d post discontinuation of treatment. Spleen and BM cells from a subset of mice in each arm are pooled and 5×106 cells/mouse (8 mice/condition) are transplanted into wild-type FVB/N recipient mice irradiated at 900 cGy. Engraftment is monitored by drawing peripheral blood (PB) every 4 weeks. The percentage of GFP+ cells in PB is analyzed by flow cytometry.

    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 2.0597 mL 10.2987 mL 20.5973 mL 51.4933 mL
    5 mM 0.4119 mL 2.0597 mL 4.1195 mL 10.2987 mL
    10 mM 0.2060 mL 1.0299 mL 2.0597 mL 5.1493 mL
    15 mM 0.1373 mL 0.6866 mL 1.3732 mL 3.4329 mL
    20 mM 0.1030 mL 0.5149 mL 1.0299 mL 2.5747 mL
    25 mM 0.0824 mL 0.4119 mL 0.8239 mL 2.0597 mL
    30 mM 0.0687 mL 0.3433 mL 0.6866 mL 1.7164 mL
    40 mM 0.0515 mL 0.2575 mL 0.5149 mL 1.2873 mL
    50 mM 0.0412 mL 0.2060 mL 0.4119 mL 1.0299 mL
    60 mM 0.0343 mL 0.1716 mL 0.3433 mL 0.8582 mL
    80 mM 0.0257 mL 0.1287 mL 0.2575 mL 0.6437 mL
    100 mM 0.0206 mL 0.1030 mL 0.2060 mL 0.5149 mL
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    Sonidegib 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:

    Sonidegib956697-53-3Erismodegib LDE225 NVP-LDE225LDE225LDE 225LDE-225SmoSmoothenedInhibitorinhibitorinhibit

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