Sonidegib

Sonidegib

Clinical data
Trade names	Odomzo
Other names	LDE225, erismodegib
AHFS/Drugs.com	Monograph
MedlinePlus	a615034
License data	EU EMA: by INN US DailyMed: Sonidegib
Pregnancy category	Contraindicated (X)
Routes of administration	By mouth
Drug class	Antineoplastic agents
ATC code	L01XJ02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only US: ℞-only EU: Rx-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	<10%
Protein binding	>97%
Metabolism	Liver (CYP3A)
Elimination half-life	~28 days
Excretion	Feces (~70%), urine (30%)
Identifiers
IUPAC name N-[6-[(2S,6R)-2,6-Dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide
CAS Number	956697-53-3 Y
PubChem CID	24775005
DrugBank	DB09143
ChemSpider	25027390
UNII	0RLU3VTK5M
KEGG	D10119 as salt: D10729
ChEBI	CHEBI:90863 Y
ChEMBL	ChEMBL2105737
CompTox Dashboard (EPA)	DTXSID501009335
Chemical and physical data
Formula	C26H26F3N3O3
Molar mass	485.507 g·mol−1
3D model (JSmol)	Interactive image
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
InChI 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+ Key: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).

Approvals and indications

It was approved for medical use in the United States and in the European Union in 2015

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.

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

Development

It has been investigated as a potential treatment for:

• Pancreatic cancer
• Breast cancer
• Basal cell carcinoma of the skin
• Small cell lung cancer
• Medulloblastoma
• Advanced solid tumors (including ovarian, breast, pancreatic, stomach, oesophageal cancers and glioblastoma multiforme)
• Acute leukemia and chronic myeloid leukemia
• Myelofibrosis and essential thrombocythaemia

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

External links

• "Sonidegib". Drug Information Portal. U.S. National Library of Medicine.
• "Sonidegib phosphate". Drug Information Portal. U.S. National Library of Medicine.