Sonidegib (LDE-225)

new

featured

    WARNING: This product is for research use only, not for human or veterinary use.

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.

Price and Availability

Sonidegib (LDE225; Erismodegib), purity > 98%, is in stock. Price updated on 10/27/2016. The same day shipping out after order is received. Note: the estimated shipping out time for order > 200mg may be 2 weeks.

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

Technical Data

Additional Information

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

References

1: Tibes R. Sonidegib phosphate: new approval for basal cell carcinoma. Drugs Today (Barc). 2016 May;52(5):295-303. doi: 10.1358/dot.2016.52.5.2470697. PubMed PMID: 27376162.

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.