crizotinib   Click here for help

GtoPdb Ligand ID: 4903

Synonyms: (R)-crizotinib | PF 2341066 | PF-02341066 | PF-2341066 | PF2341066 | Xalkori®
Approved drug PDB Ligand Immunopharmacology Ligand
crizotinib is an approved drug (FDA (2011), EMA (2012))
Compound class: Synthetic organic
Comment: Critzotinib is a Type-1 kinase inhibitor and was first approved by the FDA in 2011. It inhibits ALK, cMET and ROS1 receptor tyrosine kinases. Critzotinib is a chiral molecule that exploits the three-dimensional space of the ATP pocket to achieve optimal potency and selectivity [6]. The R-enantiomer as shown here exhibits better potency than the either the racemate or S-isomer and the approved drug should contain only the R-enantiomer.
Pfizer developed the 3rd generation ALK inhibitor lorlatinib as a follow-up to critzotinib, and this new drug has been reported to outperfom its predecessor in lung cancer.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

crizotinib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 77.99
Molecular weight 449.12
XLogP 4.83
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES Nc1ncc(cc1OC(c1c(Cl)ccc(c1Cl)F)C)c1cnn(c1)C1CCNCC1
Isomeric SMILES Nc1ncc(cc1O[C@@H](c1c(Cl)ccc(c1Cl)F)C)c1cnn(c1)C1CCNCC1
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
InChI Key KTEIFNKAUNYNJU-GFCCVEGCSA-N
Bioactivity Comments
The (S)-enantiomer ((S)-crizotinib) is considerably less potent than the (R)-enantiomer against its established protein kinase targets [4]. Interestingly, (S)-crizotinib has been reported to inhibit the activity of NUDT1 (P36639) with a Kd of 48nM [4]. NUDT1 is an antimutagenic enzyme involved in the effective elimination of oxidised nucleotides (induced by oxidative stress, for example), thus preventing their incorporation into DNA. At this target the (R)-enantiomer is the less potent enantiomer (Kd 781nM). This highlights the necessity that drug compounds be steroespecifically pure when there is a pharmacological difference in activity between stereoisomers (ie they exhibit distinct molecular mechanisms of action), as enantiomerically impure mixtures may result in off-target effects.
A number of chemical suppliers and other submitters to online chemistry databases specify the non-stereoisomeric molecule depicted in PubChem CID 11597571.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
MET proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 8.7 pKi - 1
⤷ pKi 8.7 (Ki 2x10-9 M) [1]
MET proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 9.1 pIC50 - 7
⤷ pIC50 9.1 (IC50 7.8x10-10 M) [7]
ALK receptor tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 9.0 pIC50 - 1
⤷ pIC50 9.0 (IC50 1x10-9 M) [1]
Targets where the ligand is described in the comment field
Target Comment
ALK receptor tyrosine kinase Crizotinib appears to be a selective ALK inhibitor acting on the tyrosine kinase activity [3]
Ligand mentioned in the following text fields
Type XVII RTKs: ROS receptors comments