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

Name: Sonidegib diphosphate
Brand: MedChemExpress
SKU: HY-16582
Rating: 5.0 (7 reviews)

Cat. No.: HY-16582 Purity: 99.73%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

Sonidegib diphosphate (Erismodegib 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.

Sonidegib diphosphate Chemical Structure

CAS No. : 1218778-77-8

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 83	In-stock	Estimated Time of Arrival: December 31
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10 mM * 1 mL in DMSO	USD 83	In-stock	Estimated Time of Arrival: December 31
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5 mg	USD 55	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 66	In-stock	Estimated Time of Arrival: December 31
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Based on 7 publication(s) in Google Scholar

Other Forms of Sonidegib diphosphate:

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6 Publications Citing Use of MCE Sonidegib diphosphate

: Sonidegib diphosphate 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).

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Biological Activity
Protocol
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Description

Sonidegib diphosphate (Erismodegib 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^[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.

In Vivo

Sonidegib (NVP-LDE225) is a weak base with a measured pK_a 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

681.49

Formula

C₂₆H₃₂F₃N₃O₁₁P₂

CAS No.

1218778-77-8

Appearance

Solid

Color

White to off-white

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.O=P(O)(O)O.O=P(O)(O)O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (146.74 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

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

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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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 (3.67 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 (3.67 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 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 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (3.67 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.

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: 50% PEG300 50% Saline
Solubility: 5 mg/mL (7.34 mM); Suspended solution; Need ultrasonic and warming and heat to 60°C

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

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).

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

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: 99.73%

Select Batch:

Data Sheet (282 KB) SDS (252 KB)

COA (253 KB) LCMS (113 KB)

Handling Instructions (2659 KB)

References

[1]. Pan S, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Mar 16;1(3):130-4. [Content Brief]

[2]. Irvine DA, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016 May 9;6:25476. [Content Brief]

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	[1]. Pan S, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Mar 16;1(3):130-4. [Content Brief] [2]. Irvine DA, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016 May 9;6:25476. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.4674 mL	7.3369 mL	14.6737 mL	36.6843 mL
	5 mM	0.2935 mL	1.4674 mL	2.9347 mL	7.3369 mL
	10 mM	0.1467 mL	0.7337 mL	1.4674 mL	3.6684 mL
	15 mM	0.0978 mL	0.4891 mL	0.9782 mL	2.4456 mL
	20 mM	0.0734 mL	0.3668 mL	0.7337 mL	1.8342 mL
	25 mM	0.0587 mL	0.2935 mL	0.5869 mL	1.4674 mL
	30 mM	0.0489 mL	0.2446 mL	0.4891 mL	1.2228 mL
	40 mM	0.0367 mL	0.1834 mL	0.3668 mL	0.9171 mL
	50 mM	0.0293 mL	0.1467 mL	0.2935 mL	0.7337 mL
	60 mM	0.0245 mL	0.1223 mL	0.2446 mL	0.6114 mL
	80 mM	0.0183 mL	0.0917 mL	0.1834 mL	0.4586 mL
	100 mM	0.0147 mL	0.0734 mL	0.1467 mL	0.3668 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Sonidegib diphosphate 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:

Sonidegib diphosphate1218778-77-8Erismodegib diphosphateLDE225 diphosphateNVP-LDE225 diphosphateSmoSmoothenedInhibitorinhibitorinhibit

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

Customer Review

Other Forms of Sonidegib diphosphate:

Sonidegib diphosphate Related Antibodies

6 Publications Citing Use of MCE Sonidegib diphosphate

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•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

Sonidegib diphosphate Related Antibodies

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Complete Stock Solution Preparation Table

Sonidegib diphosphate Related Classifications

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