Sonidegib Explained

Width:275
Tradename:Odomzo
Dailymedid:Sonidegib
Licence Eu:yes
Pregnancy Category:Contraindicated (X)
Routes Of Administration:By mouth
Class:Antineoplastic agents
Atc Prefix:L01
Atc Suffix:XJ02
Legal Au:S4
Legal Au Comment:[1]
Legal Ca:Rx-only
Legal Ca Comment:[2]
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Status:Rx-only
Bioavailability:<10%
Protein Bound:>97%
Metabolism:Liver (CYP3A)
Elimination Half-Life:~28 days
Excretion:Feces (~70%), urine (30%)
Index2 Label:as salt
Cas Number:956697-53-3
Pubchem:24775005
Drugbank:DB09143
Chemspiderid:25027390
Chebi:90863
Chembl:2105737
Unii:0RLU3VTK5M
Kegg:D10119
Kegg2:D10729
Synonyms:LDE225, erismodegib
Iupac Name:N-[6-[(2''S'',6''R'')-2,6-Dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide
C:26
H:26
F:3
N:3
O:3
Smiles:C[C@@H]1CN(C[C@@H](O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F
Stdinchi: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+
Stdinchikey:VZZJRYRQSPEMTK-CALCHBBNSA-N

Sonidegib (INN), sold under the brand name Odomzo, is a medication used to treat cancer.

Sonidegib is Hedgehog signaling pathway inhibitor (via smoothened antagonism).[3] [4]

Approvals and indications

It was approved for medical use in the United States and in the European Union in 2015[5] [6] [7]

It is indicated for the treatment of adults with locally advanced basal-cell carcinoma that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

Pharmacology

Sonidegib is administered by mouth. Common side effects include muscle spasms, hair loss, fatigue, abdominal pain, nausea, headache, and weight loss.[8]

Sonidegib binds to and inhibits smoothened to inhibit activation of the Hedgehog pathway. Sonidegib is primarily metabolized by CYP3A and is eliminated hepatically.[8]

Development

It has been investigated as a potential treatment for:

It has demonstrated significant efficacy against melanoma in vitro and in vivo.[27] It also demonstrated efficacy in a mouse model of pancreatic cancer.[28]

External links

Notes and References

  1. Web site: Prescription medicines: registration of new chemical entities in Australia, 2015 . Therapeutic Goods Administration (TGA) . 21 June 2022 . 10 April 2023.
  2. Web site: Summary Basis of Decision (SBD) for Odomzo . Health Canada . 23 October 2014 . 29 May 2022.
  3. Web site: LDE225 - PubChem. PubChem. National Institutes of Health. 16 February 2014.
  4. Pan S, Wu X, Jiang J, Gao W, Wan Y, Cheng D, Han D, Liu J, Englund NP, Wang Y, Peukert S, Miller-Moslin K, Yuan J, Guo R, Matsumoto M, Vattay A, Jiang Y, Tsao J, Sun F, Pferdekamper AC, Dodd S, Tuntland T, Maniara W, Kelleher JF, Yao YM, Warmuth M, Williams J, Dorsch M . 6 . Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist . ACS Medicinal Chemistry Letters . 1 . 3 . 130–4 . June 2010 . 24900187 . 4007689 . 10.1021/ml1000307 .
  5. Web site: FDA approves new treatment for most common form of advanced skin cancer. www.fda.gov. 2015-07-24. 2015-07-24. https://web.archive.org/web/20150724203724/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455862.htm. dead.
  6. Web site: FDA approves Novartis's advanced skin cancer drug. 24 July 2015 . 2015-07-24.
  7. Web site: Odomzo . European Medicines Agency . 17 September 2018 . 9 June 2020.
  8. Web site: Odomzo- sonidegib capsule . DailyMed . 29 May 2019 . 9 June 2020.
  9. Web site: A Biomarker Study to Identify Predictive Signatures of Response to LDE225 (Hedgehog Inhibitor) In Patients With Resectable Pancreatic Cancer. ClinicalTrials.gov. National Institutes of Health. 16 February 2014. 13 February 2014.
  10. Web site: Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma. ClinicalTrials.gov. National Institutes of Health. 16 February 2014. 13 February 2014.
  11. Web site: Dose-escalation, and Safety Study of LDE225 and Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer Patients. ClinicalTrials.gov. National Institutes of Health. 16 February 2014. 13 February 2014.
  12. Web site: A Pilot Study of a Hedgehog Pathway Inhibitor (LDE-225) in Surgically Resectable Pancreas Cancer. ClinicalTrials.gov. National Institutes of Health. 16 February 2014. 13 February 2014.
  13. Study With LDE225 in Combination With Docetaxel in Triple Negative (TN) Advanced Breast Cancer (ABC) Patients (EDALINE). ClinicalTrials.gov. National Institutes of Health. 13 February 2014.
  14. Web site: LDE225 in Treating Patients With Stage II-III Estrogen Receptor- and HER2-Negative Breast Cancer. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  15. Web site: A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma (BOLT). ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  16. Web site: To Evaluate the Safety, Local Tolerability, PK and PD of LDE225 on Sporadic Superficial and Nodular Skin Basal Cell Carcinomas(sBCC). ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  17. Web site: A Trial to Evaluate the Safety, Local Tolerability, Pharmacokinetics and Pharmacodynamics of LDE225 on Skin Basal Cell Carcinomas in Gorlin Syndrome Patients. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  18. Web site: Combination of the Hedgehog Inhibitor, LDE225, With Etoposide and Cisplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC). ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  19. Web site: A Phase III Study of Oral LDE225 Versus (vs) Temozolomide (TMZ) in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB). ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  20. Web site: A Phase I Dose Finding and Safety Study of Oral LDE225 in Children and a Phase II Portion to Assess Preliminary Efficacy in Recurrent or Refractory MB. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  21. Web site: Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  22. Web site: Dose Finding and Safety of Oral LDE225 in Patients With Advanced Solid Tumors. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  23. Web site: LDE225 and Paclitaxel in Solid Tumors. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  24. Web site: Study of Efficacy and Safety of LDE225 in Adult Patients With Relapsed/Refractory Acute Leukemia. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  25. Web site: Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  26. Web site: A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF. ClinicalTrials.gov. National Institutes of Health. 13 February 2014. 16 February 2014.
  27. Jalili A, Mertz KD, Romanov J, Wagner C, Kalthoff F, Stuetz A, Pathria G, Gschaider M, Stingl G, Wagner SN . 6 . NVP-LDE225, a potent and selective SMOOTHENED antagonist reduces melanoma growth in vitro and in vivo . PLOS ONE . 8 . 7 . e69064 . 30 July 2013 . 23935925 . 3728309 . 10.1371/journal.pone.0069064 . 2013PLoSO...869064J . free .
  28. Fendrich V, Wiese D, Waldmann J, Lauth M, Heverhagen AE, Rehm J, Bartsch DK . Hedgehog inhibition with the orally bioavailable Smo antagonist LDE225 represses tumor growth and prolongs survival in a transgenic mouse model of islet cell neoplasms . Annals of Surgery . 254 . 5 . 818–23; discussion 823 . November 2011 . 22042473 . 10.1097/SLA.0b013e318236bc0f . 12947375 .

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