Crizotinib

Crizotinib
Clinical data

Trade names	Xalkori
MedlinePlus	a612018
License data	EU EMA: Xalkori US FDA: Crizotinib
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	Oral
ATC code	L01XE16 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	43%
Protein binding	91%
Metabolism	Hepatic (CYP3A4/CYP3A5-mediated)
Biological half-life	42 hours
Excretion	Faeces (63%), urine (22%)
Identifiers
IUPAC name 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine
Synonyms	PF-02341066 1066
CAS Number	877399-52-5^N
PubChem CID	11626560
IUPHAR/BPS	4903
DrugBank	DB08700^Y
ChemSpider	9801307^Y
UNII	53AH36668S
KEGG	D09731^N
ChEBI	CHEBI:64310^N
ChEMBL	CHEMBL601719^Y
PDB ligand	VGH (PDBe, RCSB PDB)
ECHA InfoCard	100.166.440
Chemical and physical data
Formula	C₂₁H₂₂Cl₂FN₅O
Molar mass	450.337 g/mol
3D model (Jmol)	Interactive image
SMILES C1(=C(C=CC(=C1[C@H](OC2=C(N=CC(=C2)C3=C[N](N=C3)C4CCNCC4)N)C)Cl)F)Cl
InChI InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1^Y Key:KTEIFNKAUNYNJU-GFCCVEGCSA-N^Y
^NY (what is this?)

Crizotinib (trade name Xalkori,Pfizer) is an anti-cancer drug acting as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor, approved for treatment of some non-small cell lung carcinoma (NSCLC) in the US and some other countries, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.

Crizotinib has an aminopyridine structure, and functions as a protein kinase inhibitor by competitive binding within the ATP-binding pocket of target kinases. About 4% of patients with non-small cell lung carcinoma have a chromosomal rearrangement that generates a fusion gene between EML4 ('echinoderm microtubule-associated protein-like 4') and ALK ('anaplastic lymphoma kinase'), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype. The kinase activity of the fusion protein is inhibited by crizotinib. Patients with this gene fusion are typically younger non-smokers who do not have mutations in either the epidermal growth factor receptor gene (EGFR) or in the K-Ras gene. The number of new cases of ALK-fusion NSLC is about 9,000 per year in the U.S. and about 45,000 worldwide.

...
Wikipedia