Chemistry:Sonidegib

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Short description: Chemical compound
Sonidegib
Sonidegib.svg
Clinical data
Trade namesOdomzo
Other namesLDE225, erismodegib
AHFS/Drugs.comMonograph
MedlinePlusa615034
License data
Pregnancy
category
  • Contraindicated (X)[1]
Routes of
administration		By mouth
Drug classAntineoplastic agents
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability<10%
Protein binding>97%
MetabolismLiver (CYP3A)
Elimination half-life~28 days
ExcretionFeces (~70%), urine (30%)[1]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC26H26F3N3O3
Molar mass485.507 g·mol−1
3D model (JSmol)

Sonidegib (INN), sold under the brand name Odomzo, is a medication used to treat cancer.[1]

Sonidegib is Hedgehog signaling pathway inhibitor (via smoothened antagonism).[4][5]

Approvals and indications

It was approved for medical use in the United States and in the European Union in 2015[6][1][7][8]

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.[1]

Pharmacology

Sonidegib is administered by mouth. Common side effects include muscle spasms, hair loss, fatigue, abdominal pain, nausea, headache, and weight loss.[1]

Sonidegib binds to and inhibits smoothened to inhibit activation of the Hedgehog pathway. Sonidegib is primarily metabolized by CYP3A and is eliminated hepatically.[1]

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]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Odomzo- sonidegib capsule". 29 May 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=028312dc-d155-4fd5-8abd-6bb9f011d3cc. 
  2. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2015". 21 June 2022. https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2015. 
  3. ↑ "Summary Basis of Decision (SBD) for Odomzo". 23 October 2014. https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00490&lang=en. 
  4. ↑ "LDE225 - PubChem". PubChem. National Institutes of Health. https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=135626837. 
  5. ↑ "Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist". ACS Medicinal Chemistry Letters 1 (3): 130–4. June 2010. doi:10.1021/ml1000307. PMID 24900187. 
  6. ↑ "FDA approves new treatment for most common form of advanced skin cancer". https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455862.htm. 
  7. ↑ "FDA approves Novartis's advanced skin cancer drug". 24 July 2015. https://news.yahoo.com/fda-approves-novartiss-advanced-skin-cancer-drug-162113308--finance.html. 
  8. ↑ "Odomzo". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/odomzo. 
  9. ↑ "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. 13 February 2014. http://clinicaltrials.gov/show/NCT01911416. 
  10. ↑ "Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. http://clinicaltrials.gov/ct2/show/NCT01431794. 
  11. ↑ "Dose-escalation, and Safety Study of LDE225 and Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer Patients". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. http://clinicaltrials.gov/ct2/show/NCT02027376. 
  12. ↑ "A Pilot Study of a Hedgehog Pathway Inhibitor (LDE-225) in Surgically Resectable Pancreas Cancer". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. http://clinicaltrials.gov/ct2/show/NCT01694589. 
  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. http://clinicaltrials.gov/ct2/show/NCT02027376. 
  14. ↑ "LDE225 in Treating Patients With Stage II-III Estrogen Receptor- and HER2-Negative Breast Cancer". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. http://clinicaltrials.gov/ct2/show/NCT01757327. 
  15. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01327053. 
  16. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01033019. 
  17. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT00961896. 
  18. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01579929. 
  19. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01708174. 
  20. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01125800. 
  21. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01576666. 
  22. ↑ "Dose Finding and Safety of Oral LDE225 in Patients With Advanced Solid Tumors". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. http://clinicaltrials.gov/ct2/show/NCT00880308. 
  23. ↑ "LDE225 and Paclitaxel in Solid Tumors". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. http://clinicaltrials.gov/ct2/show/NCT01954355. 
  24. ↑ "Study of Efficacy and Safety of LDE225 in Adult Patients With Relapsed/Refractory Acute Leukemia". ClinicalTrials.gov. National Institutes of Health. 13 February 2014. http://clinicaltrials.gov/ct2/show/NCT01826214. 
  25. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01456676. 
  26. ↑ "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. http://clinicaltrials.gov/ct2/show/NCT01787552. 
  27. ↑ "NVP-LDE225, a potent and selective SMOOTHENED antagonist reduces melanoma growth in vitro and in vivo". PLOS ONE 8 (7): e69064. 30 July 2013. doi:10.1371/journal.pone.0069064. PMID 23935925. Bibcode: 2013PLoSO...869064J. 
  28. ↑ "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. doi:10.1097/SLA.0b013e318236bc0f. PMID 22042473. 

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