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

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

Technical Data

Appearance: Solid powder

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

Certificate of Analysis: View CoA: current batch, Lot#CRB50824

QC Data: View QC data: current batch, Lot#CRB50824

Safety Data Sheet (MSDS): View Material Safety Data Sheet (MSDS)

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).

Harmonized System Code: 293490

Additional Information

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

References

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2: Zhou J, Quinlan M, Glenn K, Boss H, Picard F, Castro H, Sellami D. Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers. Br J Clin Pharmacol. 2016 Jun 8. doi: 10.1111/bcp.13038. [Epub ahead of print] PubMed PMID: 27277189.

3: 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 May 18. [Epub ahead of print] PubMed PMID: 27189494.

4: Kish T, Corry L. Sonidegib (Odomzo) for the Systemic Treatment of Adults With Recurrent, Locally Advanced Basal Cell Skin Cancer. P T. 2016 May;41(5):322-5. PubMed PMID: 27162473; PubMed Central PMCID: PMC4849341.

5: Irvine DA, Zhang B, Kinstrie R, Tarafdar A, Morrison H, Campbell VL, Moka HA, Ho Y, Nixon C, Manley PW, Wheadon H, Goodlad JR, Holyoake TL, Bhatia R, Copland M. 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. doi: 10.1038/srep25476. PubMed PMID: 27157927; PubMed Central PMCID: PMC4860619.

6: Zhou J, Quinlan M, Hurh E, Sellami D. Exposure-response Analysis of Sonidegib (LDE225), an Oral Inhibitor of the Hedgehog Signaling Pathway, for Effectiveness and Safety in Patients with Advanced Solid Tumors. J Clin Pharmacol. 2016 Apr 20. doi: 10.1002/jcph.749. [Epub ahead of print] PubMed PMID: 27095306.

7: Dummer R, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, Herd RM, Kaatz M, Loquai C, Stratigos AJ, Schulze HJ, Plummer R, Gogov S, Pallaud C, Yi T, Mone M, Chang AL, Cornélis F, Kudchadkar R, Trefzer U, Lear JT, Sellami D, Migden MR. The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol. 2016 Jul;75(1):113-125.e5. doi: 10.1016/j.jaad.2016.02.1226. Epub 2016 Apr 7. PubMed PMID: 27067394.

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

9: Goel V, Hurh E, Stein A, Nedelman J, Zhou J, Chiparus O, Huang PH, Gogov S, Sellami D. Population pharmacokinetics of sonidegib (LDE225), an oral inhibitor of hedgehog pathway signaling, in healthy subjects and in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Apr;77(4):745-55. doi: 10.1007/s00280-016-2982-1. Epub 2016 Feb 22. PubMed PMID: 26898300.

10: 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.

11: 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.

12: Danial C, Sarin KY, Oro AE, Chang AL. An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib. Clin Cancer Res. 2016 Mar 15;22(6):1325-9. doi: 10.1158/1078-0432.CCR-15-1588. Epub 2015 Nov 6. PubMed PMID: 26546616; PubMed Central PMCID: PMC4794361.

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

14: Migden MR, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, Herd RM, Kudchadkar R, Trefzer U, Gogov S, Pallaud C, Yi T, Mone M, Kaatz M, Loquai C, Stratigos AJ, Schulze HJ, Plummer R, Chang AL, Cornélis F, Lear JT, Sellami D, Dummer R. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015 Jun;16(6):716-28. doi: 10.1016/S1470-2045(15)70100-2. Epub 2015 May 14. PubMed PMID: 25981810.

15: Zollinger M, Lozac'h F, Hurh E, Emotte C, Bauly H, Swart P. Absorption, distribution, metabolism, and excretion (ADME) of ¹⁴C-sonidegib (LDE225) in healthy volunteers. Cancer Chemother Pharmacol. 2014 Jul;74(1):63-75. doi: 10.1007/s00280-014-2468-y. Epub 2014 May 10. PubMed PMID: 24817600.

16: Rodon J, Tawbi HA, Thomas AL, Stoller RG, Turtschi CP, Baselga J, Sarantopoulos J, Mahalingam D, Shou Y, Moles MA, Yang L, Granvil C, Hurh E, Rose KL, Amakye DD, Dummer R, Mita AC. A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor Sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res. 2014 Apr 1;20(7):1900-9. doi: 10.1158/1078-0432.CCR-13-1710. Epub 2014 Feb 12. PubMed PMID: 24523439.