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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2D Structure
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Physico-chemical Properties
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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
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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

Large-scale screening data

DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 2,8

Key to terms and symbols Click column headers to sort
Target Name in screen Sp. Type Action Value Parameter
MET proto-oncogene, receptor tyrosine kinase MET(M1250T) Hs Inhibitor Inhibition 9.3 pKd
MET proto-oncogene, receptor tyrosine kinase MET(Y1235D) Hs Inhibitor Inhibition 8.8 pKd
MET proto-oncogene, receptor tyrosine kinase MET Hs Inhibitor Inhibition 8.7 pKd
ALK receptor tyrosine kinase ALK Hs Inhibitor Inhibition 8.5 pKd
MER proto-oncogene, tyrosine kinase MERTK Hs Inhibitor Inhibition 8.4 pKd
c-ros oncogene 1, receptor tyrosine kinase ROS1 Hs Inhibitor Inhibition 8.4 pKd
EPH receptor B6 EPHB6 Hs Inhibitor Inhibition 8.2 pKd
AXL receptor tyrosine kinase AXL Hs Inhibitor Inhibition 8.1 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(T315I)-phosphorylated Hs Inhibitor Inhibition 8.0 pKd
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1(T315I)-nonphosphorylated Hs Inhibitor Inhibition 7.9 pKd
Displaying the top 10 targets  View all targets in screen »