Ceritinib

Ceritinib
Clinical data

Pronunciation	/səˈrɪtɪnɪb/ sə-RIT-i-nib
Trade names	Zykadia
AHFS/Drugs.com	Multum Consumer Information
Pregnancy category	US: D (Evidence of risk)
Routes of administration	By mouth (capsules)
ATC code	L01XE28 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	Not determined
Protein binding	97%
Metabolism	CYP3A
Biological half-life	41 hours
Excretion	Feces (92.3%), urine (1.3%)
Identifiers
IUPAC name 5-chloro-N² -{5-methyl-4-(piperidin-4-yl)-2-[(propan-2-yl)oxy]phenyl}-N⁴-[2-(propane-2-sulfonyl)phenyl]pyrimidine-2,4-diamine
Synonyms	LDK378
CAS Number	1032900-25-6
PubChem CID	57379345
DrugBank	DB09063
ChemSpider	29315053
UNII	K418KG2GET
KEGG	D10551
ChEBI	CHEBI:78432
ChEMBL	CHEMBL2403108
PDB ligand	4MK (PDBe, RCSB PDB)
Chemical and physical data
Formula	C₂₈H₃₆ClN₅O₃S
Molar mass	558.14 g/mol
3D model (JSmol)	Interactive image
SMILES CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl
InChI InChI=1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34) Key:VERWOWGGCGHDQE-UHFFFAOYSA-N

Ceritinib (INN, trade name Zykadia /zaɪˈkeɪdiːə/ zy-KAY-dee-ə) is a drug for the treatment of a specific type of lung cancer. It is an anaplastic lymphoma kinase (ALK) inhibitor. It was developed by Novartis. It was approved in April 2014 by the Food and Drug Administration for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) in patients that failed treatment with crizotinib. It is a more effective, but more toxic, alternative to traditional platinum-based chemotherapies.

Ceritinib was found at physiological concentrations to inhibit ALK, insulin-like growth factor 1 receptor (IGF-1R), and ROS1.

Serious adverse effects include gastrointestinal toxicity, hepatotoxicity, interstitial lung disease, prolonged QT syndrome, hyperglycemia, bradycardia, and pancreatitis. The most commonly reported side effects were diarrhea, nausea, elevated liver enzymes, vomiting, abdominal pain, fatigue, decreased appetite, and constipation.

More than half of patients in clinical trials experienced adverse events that necessitated a reduction in dose.

Ceritinib was granted breakthrough status in March 2013 for ALK-positive NSCLC unresponsive to crizotinib, and FDA approval in April 2014 for the same indication.

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