crizotinib

Ligand id: 4903

Name: crizotinib

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 77.99
Molecular weight 449.12
XLogP 2.83
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

View interactive charts of activity data from ChEMBL and GtoPdb across species (New!)

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 human catalytic receptors
Key to terms and symbols Click column headers to sort
Target Type Action Affinity Units Concentration range (M) Reference
MET proto-oncogene, receptor tyrosine kinase Inhibitor Inhibition 8.7 pKi - 1
pKi 8.7 (Ki 2x10-9 M) [1]
MET proto-oncogene, receptor tyrosine kinase Inhibitor Inhibition 9.1 pIC50 - 5
pIC50 9.1 (IC50 7.8x10-10 M) [5]
ALK receptor tyrosine kinase 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
Ligand mentioned in the following text fields