Compound Detail

CHEMBL601719

CRIZOTINIB

💊 Approved Drug

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💊 Approved Drug

C[C@@H](Oc1cc(-c2cnn(C3CCNCC3)c2)cnc1N)c1c(Cl)ccc(F)c1Cl

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL601719
Name	CRIZOTINIB
Phase	Approved
Structure Type	MOL
InChI Key	KTEIFNKAUNYNJU-GFCCVEGCSA-N
Therapeutic	✓ Yes

Known Names

Crizotinib NSC-756645 PF-02341066 Pf-2341066 Xalkori

389

Targets

1,069

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

450.4

MW (Da)

5.04

ALogP

HBA

HBD

78.0

PSA (Å²)

0.53

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2011
Availability	Prescription
Chirality	Single Enantiomer

Routes of Administration

Oral

Flags

First in Class

USAN Stem	-tinib
USAN Year	2009

Extended Properties

Molecular Formula	C21H22Cl2FN5O
MW	450.35
Aromatic Rings	3
Heavy Atoms	30
NP-Likeness	-0.99

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Hepatocyte growth factor receptor inhibitor	INHIBITOR	Hepatocyte growth factor receptor	✓	✓
ALK tyrosine kinase receptor inhibitor	INHIBITOR	ALK tyrosine kinase receptor	✓	✓
EML4-ALK inhibitor	INHIBITOR	EML4-ALK	✓	✓
NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor) inhibitor	INHIBITOR	NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor)	✓	✓
Proto-oncogene tyrosine-protein kinase ROS inhibitor	INHIBITOR	Proto-oncogene tyrosine-protein kinase ROS	✓	✓
Macrophage-stimulating protein receptor inhibitor	INHIBITOR	Macrophage-stimulating protein receptor	✓	✓

Indications

Carcinoma, Non-Small-Cell Lung Neoplasms Neoplasms Adenocarcinoma of Lung Carcinoma Lung Neoplasms Adenocarcinoma Bile Duct Neoplasms Carcinoma, Renal Cell Carcinoma, Squamous Cell Endometrial Neoplasms Gallbladder Neoplasms Granuloma, Plasma Cell Leukemia, Myeloid, Acute Lymphoma, Large-Cell, Anaplastic Multiple Myeloma Neurofibromatosis 2 Stomach Neoplasms Uveal Melanoma Breast Neoplasms

ATC Classification

L01ED01

crizotinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 801 meas. best 9.29

Kd 219 meas. best 9.7

Ki 29 meas. best 9.22

EC50 20 meas. best 9.33

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Hepatocyte growth factor receptor CHEMBL3717	Kd	9.7	8.8043	0.2	7
ALK tyrosine kinase receptor CHEMBL4247	EC50	9.33	6.475	0.5	4
Hepatocyte growth factor receptor CHEMBL3717	IC50	9.29	8.3114	0.5	43
Proto-oncogene tyrosine-protein kinase ROS CHEMBL5568	Ki	9.22	8.1675	0.6	8
ALK tyrosine kinase receptor CHEMBL4247	IC50	9.19	7.1484	0.6	110
Proto-oncogene tyrosine-protein kinase ROS CHEMBL5568	IC50	9.15	8.0373	0.7	11
ALK tyrosine kinase receptor CHEMBL4247	Ki	9.13	8.48	0.7	8
Leukocyte tyrosine kinase receptor CHEMBL5627	IC50	8.74	8.74	1.8	1
NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor) CHEMBL2111387	IC50	8.7	7.995	2.0	2
Hepatocyte growth factor receptor CHEMBL3717	Ki	8.7	7.9291	2.0	11
BDNF/NT-3 growth factors receptor CHEMBL4898	IC50	8.7	7.8133	2.0	3
Unchecked CHEMBL612545	IC50	8.57	6.6465	2.7	26
ALK tyrosine kinase receptor CHEMBL4247	Kd	8.52	8.4533	3.0	3
High affinity nerve growth factor receptor CHEMBL2815	IC50	8.49	7.6975	3.2	4
Tyrosine-protein kinase receptor UFO CHEMBL4895	IC50	8.48	7.015	3.3	4
Tyrosine-protein kinase Mer CHEMBL5331	IC50	8.47	8.47	3.4	1
Tyrosine-protein kinase Mer CHEMBL5331	Kd	8.44	8.44	3.6	1
CD74-ROS1 CHEMBL4680046	IC50	8.41	8.005	3.9	2
H-2 class II histocompatibility antigen gamma chain/Proto-oncogene tyrosine-protein kinase ROS CHEMBL6066844	IC50	8.41	8.185	3.9	2
Unchecked CHEMBL612545	Ki	8.4	8.085	4.0	2
Proto-oncogene tyrosine-protein kinase ROS CHEMBL5568	Kd	8.39	8.39	4.1	1
NT-3 growth factor receptor CHEMBL5608	IC50	8.36	8.36	4.4	1
BaF3 CHEMBL614524	IC50	8.36	6.5855	4.3	22
EML4-ALK CHEMBL3883330	IC50	8.3	6.5575	5.0	40
Angiopoietin-1 receptor CHEMBL4128	IC50	8.3	7.325	5.0	2
Macrophage-stimulating protein receptor CHEMBL2689	IC50	8.26	7.2625	5.5	4
Ephrin type-B receptor 6 CHEMBL5836	Kd	8.22	7.24	6.0	2
NON-PROTEIN TARGET CHEMBL3879801	IC50	8.16	6.8165	6.9	31
EBC-1 CHEMBL4296411	IC50	8.16	7.82	6.9	3
Tyrosine-protein kinase receptor UFO CHEMBL4895	Kd	8.11	8.11	7.8	1
Muscle, skeletal receptor tyrosine-protein kinase CHEMBL5684	IC50	8.04	8.04	9.1	1
MKN-45 CHEMBL614354	IC50	8.04	7.8525	9.1	4
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	8.0	6.8156	10.0	16
SU-DHL-1 CHEMBL2366200	IC50	8.0	7.0933	10.0	3
Tyrosine-protein kinase Lck CHEMBL258	IC50	7.96	6.36	11.0	3
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	7.96	7.765	11.0	2
Tyrosine-protein kinase JAK2 CHEMBL2971	Kd	7.96	7.25	11.0	2
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	IC50	7.96	7.96	11.0	1
Leukocyte tyrosine kinase receptor CHEMBL5627	Kd	7.92	7.92	12.0	1
SNU-5 CHEMBL614934	IC50	7.8	7.39	16.0	2
ROS1-SDC4 CHEMBL5303568	IC50	7.77	7.77	17.0	1
STE20-like serine/threonine-protein kinase CHEMBL4202	Kd	7.75	6.84	18.0	2
Tyrosine-protein kinase receptor TYRO3 CHEMBL5314	IC50	7.7	7.7	20.0	1
HCC78 CHEMBL4296421	IC50	7.68	6.4922	21.0	9
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	7.62	6.78	24.0	2
Macrophage-stimulating protein receptor CHEMBL2689	Kd	7.6	7.36	25.0	2
KARPAS-299 CHEMBL2366156	IC50	7.52	6.7727	30.0	11
Tyrosine-protein kinase Lck CHEMBL258	Kd	7.52	6.685	30.0	2
Interleukin-1 receptor-associated kinase 3 CHEMBL5081	Kd	7.51	6.86	31.0	2
NON-PROTEIN TARGET CHEMBL3879801	EC50	7.5	6.4844	32.0	9

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	44.0	mL.min-1.kg-1	Homo sapiens
CL	44.0	mL.min-1.kg-1	Homo sapiens
CL	22.1	mL.min-1.g-1	Homo sapiens
CL	45.6	mL.min-1.g-1	Mus musculus
CL	44.0	mL.min-1.g-1	Homo sapiens
Fu	0.03	-	Rattus norvegicus
Fu	0.003	-	Rattus norvegicus
Fu	0.093	-	Homo sapiens
Ka	1.17	10'7/Ms	Homo sapiens
Ka	2.989	10'6/Ms	Homo sapiens
T1/2	1.047	hr	Homo sapiens
T1/2	0.5067	hr	Mus musculus
T1/2	0.1111	hr	Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Hepatocyte growth factor receptor	Kd	=	0.2	nM	9.7	Binding affinity to MET (unknown origin)	28280261
ALK tyrosine kinase receptor	EC50	=	0.47	nM	9.33	Inhibition of recombinant ALK (unknown origin) after 1 hr by fluorescence assay	30108712
Hepatocyte growth factor receptor	IC50	=	0.51	nM	9.29	Inhibition of c-MET (unknown origin) by kinome scan-based assay	31419130
Hepatocyte growth factor receptor	Kd	=	0.55	nM	9.26	Binding constant for MET(M1250T) kinase domain	22037378
Proto-oncogene tyrosine-protein kinase ROS	Ki	=	0.6	nM	9.22	Inhibition of wild type ROS1 (unknown origin)	28431340
Proto-oncogene tyrosine-protein kinase ROS	Ki	=	0.6	nM	9.22	Inhibition of ROS1 (unknown origin)	30258534
Proto-oncogene tyrosine-protein kinase ROS	Ki	=	0.6	nM	9.22	Binding affinity to recombinant human ROS1 assessed as inhibition constant in pr...	25733882
ALK tyrosine kinase receptor	IC50	=	0.64	nM	9.19	Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]AT...	27144831
Proto-oncogene tyrosine-protein kinase ROS	IC50	=	0.7	nM	9.15	Inhibition of ROS1 (unknown origin)	25461320
ALK tyrosine kinase receptor	Ki	=	0.74	nM	9.13	Inhibition of wild type human recombinant ALK kinase domain (amino acids 1093 to...	24819116
ALK tyrosine kinase receptor	Ki	=	0.74	nM	9.13	Inhibition of ALK (unknown origin)	28431340
ALK tyrosine kinase receptor	Ki	=	0.74	nM	9.13	Binding affinity to ALK (unknown origin) assessed as inhibition of constant	38389874
Hepatocyte growth factor receptor	IC50	=	0.78	nM	9.11	Inhibition of recombinant MET using biotinylated-poly(GT) peptide as substrate a...	21708465
Hepatocyte growth factor receptor	IC50	=	0.9	nM	9.05	Inhibition of c-Met (unknown origin) by ADP-Glo kinase assay	32371098
Hepatocyte growth factor receptor	IC50	=	0.9	nM	9.05	Inhibition of recombinant c-MET (unknown origin) using poly (Glu,Tyr) 4:1 as sub...	27017548
Proto-oncogene tyrosine-protein kinase ROS	IC50	=	0.95	nM	9.02	Inhibition of human N-terminal GST-fused ROS cytoplasmic domain (1883 to 2347(en...	24419060
Hepatocyte growth factor receptor	IC50	=	1.053	nM	8.98	Inhibition of human GST-tagged c-MET using KKKSPGEYVNIEFG as substrate preincuba...	29202410
ALK tyrosine kinase receptor	IC50	=	1.1	nM	8.96	Inhibition of N-terminal GST-tagged human wild type ALK cytoplasmic domain (1058...	36332597
Hepatocyte growth factor receptor	IC50	=	1.1	nM	8.96	Inhibition of c-Met (unknown origin) using poly (Glu, Tyr) 4:1 as substrate afte...	23993328
Hepatocyte growth factor receptor	IC50	=	1.4	nM	8.85	Inhibition of recombinant c-Met (unknown origin) using poly (Glu,Tyr)4:1 as subs...	26698536

Literature References

PubMed	DOI	Target Context	# Activities
18077425	10.1073/pnas.0707498104	NON-PROTEIN TARGET	205
27780853	10.1158/1078-0432.ccr-16-0569	EML4-ALK	50
27780853	10.1158/1078-0432.ccr-16-0569	Unchecked	31
19459657	10.1021/bi900438w	Hepatocyte growth factor receptor	25
27780853	10.1158/1078-0432.ccr-16-0569	ADMET	20
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
38477575	10.1021/acs.jmedchem.4c00077	MDA-MB-231	14
18077425	10.1073/pnas.0707498104	COLO	14
24432909	10.1021/jm401805h	ALK tyrosine kinase receptor	12
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
24819116	10.1021/jm500261q	ALK tyrosine kinase receptor	11
24419060	10.1158/1535-7163.mct-13-0395	Epidermal growth factor receptor	11
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
26568289	10.1021/acs.jmedchem.5b01136	NON-PROTEIN TARGET	9
27780853	10.1158/1078-0432.ccr-16-0569	BaF3	9
37861443	10.1021/acs.jmedchem.3c01090	ALK tyrosine kinase receptor	9
24419060	10.1158/1535-7163.mct-13-0395	ALK tyrosine kinase receptor	9
28431340	10.1016/j.ejmech.2017.04.032	EML4-ALK	9
26568289	10.1021/acs.jmedchem.5b01136	EML4-ALK	8
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8

Data from ChEMBL 36 via Core Engine