Sonidegib (LDE-225)
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MedKoo CAT#: 205510

CAS#: 956697-53-3 (free base)

Description: Sonidegib, also known as, erismodegib, LDE225, NVP-LDE225, is an orally bioavailable small-molecule Smoothened (Smo) antagonist with potential antineoplastic activity. Erismodegib selectively binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway and, so, the inhibition of tumor cells in which this pathway is abnormally activated. It was approved by the FDA for treating basal cell carcinoma in July 2015.


Chemical Structure

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Sonidegib (LDE-225)
CAS# 956697-53-3 (free base)

Theoretical Analysis

MedKoo Cat#: 205510
Name: Sonidegib (LDE-225)
CAS#: 956697-53-3 (free base)
Chemical Formula: C26H26F3N3O3
Exact Mass: 485.19263
Molecular Weight: 485.49815
Elemental Analysis: C, 64.32; H, 5.40; F, 11.74; N, 8.66; O, 9.89

Price and Availability

Size Price Availability Quantity
50.0mg USD 150.0 Ready to ship
100.0mg USD 250.0 Ready to ship
200.0mg USD 450.0 Ready to ship
500.0mg USD 850.0 Ready to ship
1.0g USD 1450.0 Ready to ship
2.0g USD 2250.0 Ready to ship
5.0g USD 4250.0 2 Weeks
10.0g USD 7650.0 2 Weeks
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Related CAS #: 956697-53-3 (free base)   1218778-77-8 (phosphate)    

Synonym: LDE225; LDE 225; LDE-225; NVP-LDE225; NVP-LDE-225; NVP LDE225; Erismodegib; Sonidegib; Odomzo.

IUPAC/Chemical Name: N-(6-((2R,6S)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxamide

InChi Key: VZZJRYRQSPEMTK-CALCHBBNSA-N

InChi Code: InChI=1S/C26H26F3N3O3/c1-16-14-32(15-17(2)34-16)24-12-9-20(13-30-24)31-25(33)23-6-4-5-22(18(23)3)19-7-10-21(11-8-19)35-26(27,28)29/h4-13,16-17H,14-15H2,1-3H3,(H,31,33)/t16-,17+

SMILES Code: O=C(C1=C(C)C(C2=CC=C(OC(F)(F)F)C=C2)=CC=C1)NC3=CC=C(N4C[C@@H](C)O[C@@H](C)C4)N=C3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Sonidegib (Erismodegib) is a Smo antagonist with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays.
In vitro activity: Human melanoma cell lines were treated with different concentrations of NVP-LDE225 or the vehicle (DMSO). Viability of cells was assessed by MTT assay. There was a significant reduction of cell viability after treatment of cells with NVP-LDE225 which was dose and time dependent. Decreased viability of human melanoma cell lines (LOX-IMVI, UACC-257 and MEL-FH) after NVP-LDE225 treatment was accompanied by changes in cell morphology including appearance of blebs and cell disintegration into apoptotic bodies (data not shown). This could be confirmed by annexin V staining where there was a significant induction of annexin V positive/propidium iodide negative apoptotic cells after NVP-LDE225, as compared to vehicle (DMSO) treatment (Fig. 5 and Figure S2). Reference: PLoS One. 2013 Jul 30;8(7):e69064. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728309/
In vivo activity: Whether intratumorally administered NVP-LDE225 is able to inhibit the growth of human melanoma cells was investigated in athymic Nude-Foxn1 nu/nu mice. 1×106 LOX IMVI human melanoma cells suspended in PBS containing 10% FCS were injected s.c into both flanks. As tumors reached the mean volume of 48 mm3, NVP-LDE225 was injected on daily basis at doses of 2, 20 or 200 µg/shot. NVP-LDE225 induced a significant antitumor response (p<0.05). Doses of NVP-LDE225 less than 2 µg, 0.2 and 0.02 µg showed non-significant or no antitumor response, respectively (Fig. 6 C). Immunofluorescent microscopy staining for GLI1 expression showed decreased expression upon NVP-LDE225 treatment (Fig. 7). Reference: PLoS One. 2013 Jul 30;8(7):e69064. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728309/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 73.5 151.39
Ethanol 48.0 98.87

Preparing Stock Solutions

The following data is based on the product molecular weight 485.49815 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Jalili A, Mertz KD, Romanov J, Wagner C, Kalthoff F, Stuetz A, Pathria G, Gschaider M, Stingl G, Wagner SN. NVP-LDE225, a potent and selective SMOOTHENED antagonist reduces melanoma growth in vitro and in vivo. PLoS One. 2013 Jul 30;8(7):e69064. doi: 10.1371/journal.pone.0069064. Erratum in: PLoS One. 2013;8(9). doi:10.1371/annotation/ddd22094-5d8d-43ef-ad81-b95afe392ec7. PMID: 23935925; PMCID: PMC3728309.
In vitro protocol: 1. Jalili A, Mertz KD, Romanov J, Wagner C, Kalthoff F, Stuetz A, Pathria G, Gschaider M, Stingl G, Wagner SN. NVP-LDE225, a potent and selective SMOOTHENED antagonist reduces melanoma growth in vitro and in vivo. PLoS One. 2013 Jul 30;8(7):e69064. doi: 10.1371/journal.pone.0069064. Erratum in: PLoS One. 2013;8(9). doi:10.1371/annotation/ddd22094-5d8d-43ef-ad81-b95afe392ec7. PMID: 23935925; PMCID: PMC3728309.
In vivo protocol: 1. Jalili A, Mertz KD, Romanov J, Wagner C, Kalthoff F, Stuetz A, Pathria G, Gschaider M, Stingl G, Wagner SN. NVP-LDE225, a potent and selective SMOOTHENED antagonist reduces melanoma growth in vitro and in vivo. PLoS One. 2013 Jul 30;8(7):e69064. doi: 10.1371/journal.pone.0069064. Erratum in: PLoS One. 2013;8(9). doi:10.1371/annotation/ddd22094-5d8d-43ef-ad81-b95afe392ec7. PMID: 23935925; PMCID: PMC3728309.

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1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548922/ PubMed PMID: 31644228.

2: Li Y, Song Q, Day BW. Phase I and phase II sonidegib and vismodegib clinical trials for the treatment of paediatric and adult MB patients: a systemic review and meta-analysis. Acta Neuropathol Commun. 2019 Jul 30;7(1):123. doi: 10.1186/s40478-019-0773-8. Review. PubMed PMID: 31362788; PubMed Central PMCID: PMC6668073.

3: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500869/ PubMed PMID: 29999928.

4: Sonidegib for basal cell carcinoma. Aust Prescr. 2018 Jun;41(3):94. doi: 10.18773/austprescr.2018.025. Epub 2018 May 15. Review. PubMed PMID: 29922006; PubMed Central PMCID: PMC6003011.

5: Jain S, Song R, Xie J. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas. Onco Targets Ther. 2017 Mar 16;10:1645-1653. doi: 10.2147/OTT.S130910. eCollection 2017. Review. PubMed PMID: 28352196; PubMed Central PMCID: PMC5360396.

6: Wahid M, Jawed A, Dar SA, Mandal RK, Haque S. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma. Onco Targets Ther. 2017 Jan 24;10:515-520. doi: 10.2147/OTT.S97713. eCollection 2017. Review. PubMed PMID: 28182134; PubMed Central PMCID: PMC5279825.

7: Doan HQ, Silapunt S, Migden MR. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma. Onco Targets Ther. 2016 Sep 14;9:5671-5678. eCollection 2016. Review. PubMed PMID: 27695345; PubMed Central PMCID: PMC5028081.

8: Collier NJ, Ali FR, Lear JT. The safety and efficacy of sonidegib for the treatment of locally advanced basal cell carcinoma. Expert Rev Anticancer Ther. 2016 Oct;16(10):1011-8. doi: 10.1080/14737140.2016.1230020. Epub 2016 Sep 22. Review. PubMed PMID: 27636236.

9: Ramelyte E, Amann VC, Dummer R. Sonidegib for the treatment of advanced basal cell carcinoma. Expert Opin Pharmacother. 2016 Oct;17(14):1963-8. doi: 10.1080/14656566.2016.1225725. Epub 2016 Aug 29. Review. PubMed PMID: 27538055.

10: Chen L, Silapunt S, Migden MR. Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update. Future Oncol. 2016 Sep;12(18):2095-105. doi: 10.2217/fon-2016-0118. Epub 2016 May 18. Review. PubMed PMID: 27189494.

11: Sonidegib (Odomzo) for basal cell carcinoma. Med Lett Drugs Ther. 2016 Feb 29;58(1489):31-2. Review. PubMed PMID: 26938701.

12: Burness CB, Scott LJ. Sonidegib: A Review in Locally Advanced Basal Cell Carcinoma. Target Oncol. 2016 Apr;11(2):239-46. doi: 10.1007/s11523-016-0418-9. Review. PubMed PMID: 26867946.

13: Wahid M, Jawed A, Mandal RK, Dar SA, Khan S, Akhter N, Haque S. Vismodegib, itraconazole and sonidegib as hedgehog pathway inhibitors and their relative competencies in the treatment of basal cell carcinomas. Crit Rev Oncol Hematol. 2016 Feb;98:235-41. doi: 10.1016/j.critrevonc.2015.11.006. Epub 2015 Nov 21. Review. PubMed PMID: 26614022.

14: Burness CB. Sonidegib: First Global Approval. Drugs. 2015 Sep;75(13):1559-66. doi: 10.1007/s40265-015-0458-y. Review. PubMed PMID: 26323341.



Additional Information

Related CAS#
CAS# 956697-53-3 (Sonidegib free base).
CAS# 1218778-77-8 (Sonidegib phosphate)