1. Stem Cell/Wnt
  2. Smo
  3. Erismodegib diphosphate

Erismodegib diphosphate (Synonyms: Sonidegib diphosphate; LDE225 diphosphate; NVP-LDE 225 diphosphate)

Cat. No.: HY-16582 Purity: 99.83%
Handling Instructions

Erismodegib diphosphate (Sonidegib diphosphate) 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.

Erismodegib diphosphate Chemical Structure

Erismodegib diphosphate Chemical Structure

CAS No. : 1218778-77-8

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10 mM * 1 mL in DMSO USD 90 In-stock
Estimated Time of Arrival: December 31
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10 mg USD 84 In-stock
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50 mg USD 180 In-stock
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100 mg USD 300 In-stock
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Customer Review

Based on 5 publication(s) in Google Scholar

Other Forms of Erismodegib diphosphate:

Top Publications Citing Use of Products

    Erismodegib diphosphate purchased from MCE. Usage Cited in: J Genet Genomics. 2018 May 20;45(5):237-246.

    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

    Erismodegib diphosphate (Sonidegib diphosphate) 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.

    IC50 & Target

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

    In Vitro

    The IC50 values for Erismodegib diphosphate (Sonidegib diphosphate) for the major human CYP450 drug metabolizing enzymes is greater than 10 μM[1]. Erismodegib diphosphate, 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). Erismodegib 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)±Erismodegib 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 Erismodegib (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01)[2].

    In Vivo

    Erismodegib diphosphate (Sonidegib diphosphate) 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, Erismodegib diphosphate 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, Erismodegib diphosphate 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, Erismodegib 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 Erismodegib diphosphate+ Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to Erismodegib or Nilotinib alone[2].

    Clinical Trial
    Molecular Weight

    681.49

    Formula

    C₂₆H₃₂F₃N₃O₁₁P₂

    CAS No.

    1218778-77-8

    SMILES

    O=C(C1=C(C)C(C(C=C2)=CC=C2OC(F)(F)F)=CC=C1)NC3=CC=C(N=C3)N4C[[email protected]@H](C)O[[email protected]@H](C)C4.O=P(O)(O)O.O=P(O)(O)O

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (146.74 mM; Need ultrasonic)

    H2O : 0.25 mg/mL (0.37 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.4674 mL 7.3369 mL 14.6737 mL
    5 mM 0.2935 mL 1.4674 mL 2.9347 mL
    10 mM 0.1467 mL 0.7337 mL 1.4674 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

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

      Solubility: ≥ 2.5 mg/mL (3.67 mM); Clear solution

    • 2.

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

      Solubility: ≥ 2.5 mg/mL (3.67 mM); Clear solution

    • 3.

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

      Solubility: ≥ 2.5 mg/mL (3.67 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [2]

    CD34+ CP-CML cells are seeded in SFM alone±Erismodegib±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 Erismodegib 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), Erismodegib (80 mg/kg by gavage, daily), Erismodegib+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

    Purity: 99.83%

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    Keywords:

    Erismodegib diphosphateSonidegib diphosphateLDE225 diphosphateNVP-LDE 225 diphosphateSmoSmoothenedInhibitorinhibitorinhibit

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    Cat. No.:
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