Sonidegib

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

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)[1]
Routes of administration	By mouth
Drug class	Antineoplastic agents
ATC code	L01XJ02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[2] CA: ℞-only[3] US: ℞-only[1] 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%)[1]
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 is a 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:

• Pancreatic cancer^{[9][10][11][12]}
• Breast cancer^[13][14]
• Basal cell carcinoma of the skin^[15][16][17]
• Small cell lung cancer^[18]
• Medulloblastoma^[19][20]
• Advanced solid tumors (including ovarian, breast, pancreatic, stomach, oesophageal cancers and glioblastoma multiforme)^[21][22][23]
• Acute leukemia^[24] and chronic myeloid leukemia^[25]
• Myelofibrosis and essential thrombocythaemia^[26]

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]