LDE-225 diphosphate

  • CAT Number: I009555
  • CAS Number: 1218778-77-8
  • Molecular Formula: C₂₆H₃₂F₃N₃O₁₁P₂
  • Molecular Weight: 681.49
  • Purity: ≥95%
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LDE-225 diphosphate(Cat No.:I009555), also known as Sonidegib, is a pharmacological compound that functions as a potent inhibitor of the Hedgehog signaling pathway. By targeting the Smoothened receptor, it effectively blocks the aberrant activation of this pathway. LDE-225 diphosphate has shown promise in the treatment of basal cell carcinoma (BCC) and has been evaluated in clinical trials. As a therapeutic agent, it offers the potential for inhibiting the growth and proliferation of cancer cells by interfering with the Hedgehog signaling pathway. LDE-225 diphosphate represents a valuable tool for research and development in the field of cancer therapeutics.

Catalog Number I009555
CAS Number 1218778-77-8
Molecular Formula

C₂₆H₃₂F₃N₃O₁₁P₂

Purity 95%
Target Smoothened
Solubility Soluble in DMSO
Storage Store at -20°C
Related CAS 956697-53-3(free base)
IUPAC Name N-[6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide;phosphoric acid
InChI InChI=1S/C26H26F3N3O3.2H3O4P/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;2*1-5(2,3)4/h4-13,16-17H,14-15H2,1-3H3,(H,31,33);2*(H3,1,2,3,4)/t16-,17+;;
InChIKey RWIVSVMMGFFZIJ-VWDRLOGHSA-N
SMILES CC1CN(CC(O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F.OP(=O)(O)O.OP(=O)(O)O
Reference

1: Einolf HJ, Zhou J, Won C, Wang L, Rebello S. A Physiologically-Based
Pharmacokinetic Modeling Approach To Predict Drug-Drug Interactions of Sonidegib
(LDE225) with Perpetrators of CYP3A in Cancer Patients. Drug Metab Dispos. 2017
Apr;45(4):361-374. doi: 10.1124/dmd.116.073585. Epub 2017 Jan 25. PubMed PMID:
28122787.<br />
2: Quinlan M, Zhou J, Hurh E, Sellami D. Exposure-QT analysis for sonidegib
(LDE225), an oral inhibitor of the hedgehog signaling pathway, for measures of
the QT prolongation potential in healthy subjects and in patients with advanced
solid tumors. Eur J Clin Pharmacol. 2016 Dec;72(12):1427-1432. Epub 2016 Sep 23.
PubMed PMID: 27663457.<br />
3: Pietanza MC, Litvak AM, Varghese AM, Krug LM, Fleisher M, Teitcher JB, Holodny
AI, Sima CS, Woo KM, Ng KK, Won HH, Berger MF, Kris MG, Rudin CM. A phase I trial
of the Hedgehog inhibitor, sonidegib (LDE225), in combination with etoposide and
cisplatin for the initial treatment of extensive stage small cell lung cancer.
Lung Cancer. 2016 Sep;99:23-30. doi: 10.1016/j.lungcan.2016.04.014. Epub 2016 Apr
26. PubMed PMID: 27565909.<br />
4: 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.<br />
5: 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
Nov;56(11):1406-1415. doi: 10.1002/jcph.749. PubMed PMID: 27095306.<br />
6: 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.<br />
7: 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.

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