Crizotinib

Summary

Crizotinib (CHEMBL601719) is an approved small-molecule antineoplastic agent (ATC L01ED01) targeting MET and ALK; indicated across 25 conditions including non-small cell lung carcinoma and neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01ED01
• Targets: 2 (MET, ALK)
• Indications: 25 conditions
• Clinical trials: 114
• Chemistry: 450.3 Da · C21H22Cl2FN5O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL601719
Name	Crizotinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11626560
ChEBI	CHEBI:64310
ATC	L01ED01
Molecular formula	C21H22Cl2FN5O
Molecular weight	450.3
InChIKey	KTEIFNKAUNYNJU-GFCCVEGCSA-N

SMILES: C[C@H](C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N

IUPAC name: 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine

ChEBI definition: A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)

Pharmacological roles (ChEBI): antineoplastic agent, biomarker, EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor.

Also known as: Crizotinib, NSC-756645, PF-02341066, Pf-2341066, Xalkori, CRIZOTINIB, crizotinib, (R)-Crizotinib, CRIZOTINIB (PF-02341066), (S)-crizotinib, Crizotinib (PF-02341066), CRIZOTINIB-(S)

Patent coverage: 6,134 distinct patent families (14,403 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 13,664 (95%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
MET	MET proto-oncogene, receptor tyrosine kinase	Inhibition	8.7	2.4%	P08581
ALK	ALK receptor tyrosine kinase	Inhibition	9	0.8%	Q9UM73

Broader ChEMBL bioactivity targets: 195 (assay-derived). Sample: Homeodomain-interacting protein kinase 4, Serine/threonine-protein kinase TAO2, Mitogen-activated protein kinase kinase kinase 13, Mitogen-activated protein kinase kinase kinase 15, Serine/threonine-protein kinase SBK1, Macrophage-stimulating protein receptor, Receptor-interacting serine/threonine-protein kinase 3, 5-hydroxytryptamine receptor 2B, Tyrosine-protein kinase Fyn, Macrophage colony-stimulating factor 1 receptor.

Bioactivity

ChEMBL activities: 546 potent at pChembl ≥ 5 of 559 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MET	9.7	Kd	0.2	nM	CHEMBL_ACT_16844122
ALK	9.33	EC50	0.47	nM	CHEMBL_ACT_18746624
MET	9.29	IC50	0.51	nM	CHEMBL_ACT_19145486
MET	9.26	Kd	0.55	nM	CHEMBL_ACT_7569622
ROS1	9.22	Ki	0.6	nM	CHEMBL_ACT_18761125
ROS1	9.22	Ki	0.6	nM	CHEMBL_ACT_22424893
ROS1	9.22	Ki	0.6	nM	CHEMBL_ACT_26314017
ALK	9.19	IC50	0.64	nM	CHEMBL_ACT_16635910
ROS1	9.15	IC50	0.7	nM	CHEMBL_ACT_15156272
ALK	9.13	Ki	0.74	nM	CHEMBL_ACT_14722318
ALK	9.13	Ki	0.74	nM	CHEMBL_ACT_18761137
ALK	9.13	Ki	0.74	nM	CHEMBL_ACT_25683765
MET	9.11	IC50	0.78	nM	CHEMBL_ACT_6302080
MET	9.05	IC50	0.9	nM	CHEMBL_ACT_16542778
MET	9.05	IC50	0.9	nM	CHEMBL_ACT_20683595
ROS1	9.02	IC50	0.95	nM	CHEMBL_ACT_26241364
MET	8.98	IC50	1.05	nM	CHEMBL_ACT_18368834
MET	8.96	IC50	1.1	nM	CHEMBL_ACT_13499593
ALK	8.96	IC50	1.1	nM	CHEMBL_ACT_25015179
MET	8.85	IC50	1.4	nM	CHEMBL_ACT_16461534
MET	8.82	IC50	1.5	nM	CHEMBL_ACT_18250468
ALK	8.82	IC50	1.5	nM	CHEMBL_ACT_26241328
MET	8.82	IC50	1.5	nM	CHEMBL_ACT_26241358
MET	8.82	Kd	1.5	nM	CHEMBL_ACT_7569623
MET	8.8	IC50	1.6	nM	CHEMBL_ACT_10983061
ALK	8.74	IC50	1.8	nM	CHEMBL_ACT_19230952
ALK	8.74	IC50	1.8	nM	CHEMBL_ACT_26241330
LTK	8.74	IC50	1.8	nM	CHEMBL_ACT_26241354
MET	8.7	IC50	2	nM	CHEMBL_ACT_15000972
MET	8.7	Ki	2	nM	CHEMBL_ACT_19145423

Target pathways

Aggregated over 2 target gene(s): MET, ALK.

Top Reactome pathways

57 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	ALK, MET
Disease	2	ALK, MET
Diseases of signal transduction by growth factor receptors and second messengers	2	ALK, MET
Signaling by Receptor Tyrosine Kinases	2	ALK, MET
PIP3 activates AKT signaling	1	MET
Developmental Biology	1	MET
Negative regulation of the PI3K/AKT network	1	MET
Signaling by ALK	1	ALK
Generic Transcription Pathway	1	MET
PI3K/AKT Signaling in Cancer	1	MET
Constitutive Signaling by Aberrant PI3K in Cancer	1	MET
Semaphorin interactions	1	MET
Sema4D in semaphorin signaling	1	MET
Sema4D mediated inhibition of cell attachment and migration	1	MET
Axon guidance	1	MET
Infectious disease	1	MET
RAF/MAP kinase cascade	1	MET
MAPK family signaling cascades	1	MET
MAPK1/MAPK3 signaling	1	MET
Signaling by MET	1	MET
MET Receptor Activation	1	MET
Negative regulation of MET activity	1	MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	MET
RNA Polymerase II Transcription	1	MET
Gene expression (Transcription)	1	MET
MET activates RAS signaling	1	MET
MET activates PI3K/AKT signaling	1	MET
MET activates PTPN11	1	MET
MET activates PTK2 signaling	1	MET
InlB-mediated entry of Listeria monocytogenes into host cell	1	MET

Dominant GO biological processes

GO term	Targets
cell surface receptor protein tyrosine kinase signaling pathway	2
protein phosphorylation	2
signal transduction	2
endothelial cell morphogenesis	1
liver development	1
cell surface receptor signaling pathway	1
negative regulation of autophagy	1
neuron differentiation	1
pancreas development	1
positive regulation of transcription by RNA polymerase II	1
hepatocyte growth factor receptor signaling pathway	1
branching morphogenesis of an epithelial tube	1
positive chemotaxis	1
excitatory postsynaptic potential	1
semaphorin-plexin signaling pathway	1

Indications & clinical

Indications

25 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
non-small cell lung carcinoma	4	MONDO:0005233	EFO:0003060
neoplasm	4	MONDO:0005070	EFO:0000616
lung adenocarcinoma	3	MONDO:0005061	EFO:0000571
lung neoplasm	3	MONDO:0021117	MONDO:0008903
carcinoma	3	MONDO:0004993	EFO:0000313
papillary renal cell carcinoma	2	MONDO:0017884	EFO:0000640
acute myeloid leukemia	2	MONDO:0018874	EFO:0000222
adenocarcinoma	2	MONDO:0004970	EFO:0000228
squamous cell carcinoma	2	MONDO:0005096	EFO:0000707
anaplastic large cell lymphoma	2	MONDO:0020325	EFO:0003032
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
inflammatory myofibroblastic tumor	2	MONDO:0015798	MONDO:0015798
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
endometrium neoplasm	2	MONDO:0021251	MONDO:0011962
bile duct carcinoma	2	MONDO:0005496	EFO:0005540
uveal melanoma	2	MONDO:0006486	EFO:1000616
gallbladder neoplasm	2	MONDO:0021253	MONDO:0005411
glioblastoma	1	MONDO:0018177	EFO:0000519
kidney disorder	1	MONDO:0005240	EFO:0003086
diffuse intrinsic pontine glioma	1	MONDO:0006033	EFO:1000026
breast neoplasm	1	MONDO:0021100	MONDO:0007254
colorectal neoplasm	1	MONDO:0005335	MONDO:0005575

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 114.

Phase distribution

Phase	Trials
PHASE2	38
PHASE1	32
PHASE3	18
Not specified	12
PHASE1/PHASE2	7
PHASE4	4
PHASE2/PHASE3	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05160922	PHASE4	ACTIVE_NOT_RECRUITING	Crizotinib Continuation Clinical Study
NCT02487316	PHASE4	WITHDRAWN	A Study of Treatment ALK(+) Systemic Anaplastic Large Cell Lymphoma With Crizotinib
NCT03672643	PHASE4	TERMINATED	Long Term Safety Observation of Crizotinib in Chinese NSCLC Population
NCT03707847	PHASE4	UNKNOWN	Crizotinib Combined With Etoposide Capsule Followed by Auto-HSCT for Relapsed and Refractory ALK+ ALCL
NCT02201992	PHASE3	ACTIVE_NOT_RECRUITING	Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)
NCT02767804	PHASE3	ACTIVE_NOT_RECRUITING	eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients
NCT02838420	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate and Compare the Efficacy and Safety of Alectinib Versus Crizotinib and to Evaluate the Pharmacokinetics of Alectinib in Asian Participants With Treatment-Naive Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
NCT03052608	PHASE3	ACTIVE_NOT_RECRUITING	A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC
NCT03194893	PHASE3	ACTIVE_NOT_RECRUITING	A Rollover Study of Alectinib in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive or Rearranged During Transfection (RET)-Positive Cancer
NCT04603807	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases
NCT05987332	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma
NCT06082635	PHASE3	ACTIVE_NOT_RECRUITING	TGRX-326 Chinese Phase III for Advanced Non-small Cell Lung Cancer (NSCLC)
NCT06140836	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)
NCT06254599	PHASE3	NOT_YET_RECRUITING	A Study Of SY-3505 Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC
NCT06564324	PHASE3	RECRUITING	A Phase III Study Comparing Taletrectinib With Standard Therapy in ROS1 Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients
NCT06569420	PHASE3	ACTIVE_NOT_RECRUITING	Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLC
NCT00932893	PHASE3	COMPLETED	An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene
NCT01639001	PHASE3	COMPLETED	A Study Of Crizotinib Versus Chemotherapy In Previously Untreated ALK Positive East Asian Non-Small Cell Lung Cancer Patients
NCT02075840	PHASE3	COMPLETED	A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants
NCT02737501	PHASE3	COMPLETED	ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants
NCT03874273	PHASE2/PHASE3	UNKNOWN	Study of Crizotinib in Children and Adolescents With Myofibroblastic Tumors
NCT04009317	PHASE3	UNKNOWN	Study of TQ-B3139 Versus Crizotinib in the First Line Treatment of Subjects With Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC)
NCT04632758	PHASE3	UNKNOWN	Study Comparing WX-0593 to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients
NCT05204628	PHASE3	UNKNOWN	A Study to Evaluate and Compare the Efficacy and Safety of XZP-3621 Versus Crizotinib
NCT02465060	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT02925234	PHASE2	RECRUITING	The Drug Rediscovery Protocol (DRUP Trial)
NCT03297606	PHASE2	RECRUITING	Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
NCT03947385	PHASE1/PHASE2	RECRUITING	Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
NCT04084717	PHASE2	RECRUITING	Study of Crizotinib for ROS1 and MET Activated Lung Cancer
NCT04322578	PHASE2	RECRUITING	Crizotinb or Standard Chemotherapy in Met Exon 14 Skipping Advanced NSCLC
NCT04322890	PHASE2	RECRUITING	Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation
NCT04423185	PHASE2	RECRUITING	PLATFORM Study of Precision Medicine for Rare Tumors
NCT04439253	PHASE2	ACTIVE_NOT_RECRUITING	Testing Crizotinib as a Potential Targeted Treatment in Cancers With ROS1 Genetic Changes (MATCH-Subprotocol G)
NCT04439266	PHASE2	ACTIVE_NOT_RECRUITING	Testing Crizotinib as a Potential Targeted Treatment in Cancers With ALK Genetic Changes (MATCH-Subprotocol F)
NCT05014464	PHASE2	RECRUITING	ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma
NCT05725200	PHASE2	RECRUITING	Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer
NCT06357975	PHASE2	ACTIVE_NOT_RECRUITING	Testing Crizotinib as Potentially Targeted Treatment in Cancers With MET Genetic Changes (MATCH - Subprotocol C1)
NCT06360575	PHASE2	ACTIVE_NOT_RECRUITING	Testing Crizotinib as Potentially Targeted Treatment in Cancers With MET Exon 14 Deletion Genetic Changes (MATCH - Subprotocol C2)
NCT06563999	PHASE2	RECRUITING	Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.
NCT00932451	PHASE2	COMPLETED	An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

102 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	ALK, MET
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	ALK, MET
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	ALK, MET
BOSUTINIB	ChEMBL	Phase 4 (approved)	ALK, MET
BRIGATINIB	ChEMBL	Phase 4 (approved)	ALK, MET
CERITINIB	ChEMBL	Phase 4 (approved)	ALK, MET
ENTRECTINIB	ChEMBL	Phase 4 (approved)	ALK, MET
ERLOTINIB	ChEMBL	Phase 4 (approved)	ALK, MET
FEDRATINIB	ChEMBL	Phase 4 (approved)	ALK, MET
INFIGRATINIB	ChEMBL	Phase 4 (approved)	ALK, MET
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	ALK, MET
NINTEDANIB	ChEMBL	Phase 4 (approved)	ALK, MET
PALBOCICLIB	ChEMBL	Phase 4 (approved)	ALK, MET
SUNITINIB	ChEMBL	Phase 4 (approved)	ALK, MET
VANDETANIB	ChEMBL	Phase 4 (approved)	ALK, MET
CANERTINIB	ChEMBL	Phase 3	ALK, MET
CEDIRANIB	ChEMBL	Phase 3	ALK, MET
DACTOLISIB	ChEMBL	Phase 3	ALK, MET
LESTAURTINIB	ChEMBL	Phase 3	ALK, MET
LINIFANIB	ChEMBL	Phase 3	ALK, MET
QUERCETIN	ChEMBL	Phase 3	ALK, MET
BEMCENTINIB	ChEMBL	Phase 2	ALK, MET
BI-2536	ChEMBL	Phase 2	ALK, MET
BMS-754807	ChEMBL	Phase 2	ALK, MET
CENISERTIB	ChEMBL	Phase 2	ALK, MET
ENVONALKIB	ChEMBL	Phase 2	ALK, MET
FORETINIB	ChEMBL	Phase 2	ALK, MET
ILORASERTIB	ChEMBL	Phase 2	ALK, MET
OSI-632	ChEMBL	Phase 2	ALK, MET
PELITINIB	ChEMBL	Phase 2	ALK, MET
R-406	ChEMBL	Phase 2	ALK, MET
SU-014813	ChEMBL	Phase 2	ALK, MET
TOZASERTIB	ChEMBL	Phase 2	ALK, MET
Idelalisib	PubChem	Approved	ALK, MET
Selumetinib	PubChem	Approved	ALK, MET
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	MET
ALECTINIB	ChEMBL	Phase 4 (approved)	ALK
AXITINIB	ChEMBL	Phase 4 (approved)	MET
CABOZANTINIB	ChEMBL	Phase 4 (approved)	MET
CABOZANTINIB S-MALATE	ChEMBL	Phase 4 (approved)	MET
CAPMATINIB	ChEMBL	Phase 4 (approved)	MET
DABRAFENIB	ChEMBL	Phase 4 (approved)	MET
ENSARTINIB	ChEMBL	Phase 4 (approved)	MET
GILTERITINIB	ChEMBL	Phase 4 (approved)	ALK
LORLATINIB	ChEMBL	Phase 4 (approved)	ALK
NERATINIB	ChEMBL	Phase 4 (approved)	MET
OSIMERTINIB	ChEMBL	Phase 4 (approved)	ALK
REPOTRECTINIB	ChEMBL	Phase 4 (approved)	ALK
RUXOLITINIB	ChEMBL	Phase 4 (approved)	ALK
SORAFENIB	ChEMBL	Phase 4 (approved)	MET
TEPOTINIB	ChEMBL	Phase 4 (approved)	MET
TIVOZANIB	ChEMBL	Phase 4 (approved)	MET
UPADACITINIB	ChEMBL	Phase 4 (approved)	ALK
ALVOCIDIB	ChEMBL	Phase 3	ALK
DOVITINIB	ChEMBL	Phase 3	ALK
ENZASTAURIN	ChEMBL	Phase 3	MET
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	MET
LINSITINIB	ChEMBL	Phase 3	MET
POZIOTINIB	ChEMBL	Phase 3	MET
RIGOSERTIB	ChEMBL	Phase 3	MET