Crizotinib acetate

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H22Cl2FN5O.C2H4O2
Molecular Weight	510.389
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)=O.C[C@@H](OC1=CC(=CN=C1N)C2=CN(N=C2)C3CCNCC3)C4=C(Cl)C=CC(F)=C4Cl

InChI

InChIKey=LFCVDLCLKZRGFW-UTONKHPSSA-N

InChI=1S/C21H22Cl2FN5O.C2H4O2/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;1-2(3)4/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27);1H3,(H,3,4)/t12-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C2H4O2
Molecular Weight	60.052
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C21H22Cl2FN5O
Molecular Weight	450.337
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm376058.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202570s006lbl.pdf; https://www.mskcc.org/cancer-care/clinical-trials/14-063

Crizotinib (trade name Xalkori, Pfizer, Inc.) is an anti cancer drug approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d’Origine Nantais (RON). Common adverse reactions in clinical trials with crizotinib, occurring at an incidence of 25% or higher, included visual disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue. Crizotinib is currently under investigational study for use in treatment of Uveal Melanoma.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
ALK tyrosine kinase receptor 24 Target ID: CHEMBL4247 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202570s006lbl.pdf	Inhibitor 8504		24.0 nM [IC50]
Hepatocyte growth factor receptor 56 Target ID: CHEMBL3717 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202570s006lbl.pdf	Inhibitor 8504		11.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic non-small cell lung cancer 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202570s000lbl.pdf	Primary		Approved 8583	XALKORI Approved Use Indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Launch Date 2011

C_max

Value	Dose	Analyte	Population
475 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31778074	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
87 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
327 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
328 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	250 mg 2 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
99.6 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24990113	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	CRIZOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
3240 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31778074	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1817 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3084 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3054 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	250 mg 2 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2321 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24990113	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	CRIZOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
42 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CRIZOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
29 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24990113	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CRIZOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
9.3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf			CRIZOTINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 2 times / day steady, oral Dose: 300 mg, 2 times / day Route: oral Route: steady Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31778074	unhealthy, 49 years Health Status: unhealthy Age Group: 49 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/31778074	Disc. AE: Fatigue... AEs leading to discontinuation/dose reduction: Fatigue (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31778074
250 mg 2 times / day steady, oral Recommended\|MTD Dose: 250 mg, 2 times / day Route: oral Route: steady Dose: 250 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf	unhealthy, 51 years (range: 21-79 years) Health Status: unhealthy Age Group: 51 years (range: 21-79 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf	Disc. AE: Autoimmune thyroiditis... AEs leading to discontinuation/dose reduction: Autoimmune thyroiditis (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf
250 mg 2 times / day steady, oral Recommended\|MTD Dose: 250 mg, 2 times / day Route: oral Route: steady Dose: 250 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf	unhealthy, 52 years (range: 29-82 years) Health Status: unhealthy Age Group: 52 years (range: 29-82 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf	Disc. AE: ALT increased, Pneumonitis... AEs leading to discontinuation/dose reduction: ALT increased (2.2%) Pneumonitis (1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf

AEs

AE	Significance	Dose	Population
Fatigue	grade 3, 1 patient Disc. AE	300 mg 2 times / day steady, oral Dose: 300 mg, 2 times / day Route: oral Route: steady Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31778074	unhealthy, 49 years Health Status: unhealthy Age Group: 49 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/31778074
Autoimmune thyroiditis	1 patient Disc. AE	250 mg 2 times / day steady, oral Recommended\|MTD Dose: 250 mg, 2 times / day Route: oral Route: steady Dose: 250 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf	unhealthy, 51 years (range: 21-79 years) Health Status: unhealthy Age Group: 51 years (range: 21-79 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf
Pneumonitis	1.5% Disc. AE	250 mg 2 times / day steady, oral Recommended\|MTD Dose: 250 mg, 2 times / day Route: oral Route: steady Dose: 250 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf	unhealthy, 52 years (range: 29-82 years) Health Status: unhealthy Age Group: 52 years (range: 29-82 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf
ALT increased	2.2% Disc. AE	250 mg 2 times / day steady, oral Recommended\|MTD Dose: 250 mg, 2 times / day Route: oral Route: steady Dose: 250 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf	unhealthy, 52 years (range: 29-82 years) Health Status: unhealthy Age Group: 52 years (range: 29-82 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 227 P-gp 1741 CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 OATP1B1 1079 OATP1B3 961 BCRP 910 Ca2+ channels 59 L-type Ca2+ channels 28 Nav1.5 116	CYP3A5 446 CYP2C19 1119 CYP2C8 810 CYP1A2 1197 P-gp 2052	CYP3A 142 CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
CYP3A 317	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	weak [IC50 44 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	weak [IC50 48 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	weak [Inhibition 30 uM]
Ca2+ channels 62	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf	yes [IC50 0.83 uM]
L-type Ca2+ channels 30	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf	yes [IC50 14.6 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 22 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 23 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 5.79 uM]
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 7.3 uM]	yes (co-administration study) Comment: crizotinib increased AUC of midazolam by 3.7x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes	no (co-administration study) Comment: effect is masked by inhibition Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	major	yes (co-administration study) Comment: ketoconazole increased cmax of crizotinib by 44%, auc by 216% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	major	yes (co-administration study) Comment: ketoconazole increased cmax of crizotinib by 44%, auc by 216% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	minor
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	minor
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 119	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:64310	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:64310
eMolecules	31526065	https://www.emolecules.com/cgi-bin/more?vid=31526065
MolPort	MolPort-009-679-404	https://www.molport.com/shop/molecule-link/MolPort-009-679-404
Selleck Chemicals	PF-2341066	http://www.selleckchem.com/products/PF-2341066.html
ZINC	ZINC000035902489	http://zinc15.docking.org/substances/ZINC000035902489

PubMed

Title	Date	PubMed
Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.	2015-01-05	25569083
Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy.	2014-04-10	24695225
Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes.	2013-10-01	23707608
Crizotinib for the treatment of non-small-cell lung cancer.	2013-06-01	23686600
Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC).	2013-05	22703830
Development and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors.	2013-04	23134735
Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.	2013-03	23104988
Prediction of crizotinib-midazolam interaction using the Simcyp population-based simulator: comparison of CYP3A time-dependent inhibition between human liver microsomes versus hepatocytes.	2013-02	23129213
Overcoming erlotinib resistance with tailored treatment regimen in patient-derived xenografts from naïve Asian NSCLC patients.	2013-01-15	22948846
Enhancement of the antiproliferative activity of gemcitabine by modulation of c-Met pathway in pancreatic cancer.	2013	22973962
Anaplastic Lymphoma Kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells.	2012-12-13	22286764
Adenocarcinoma of the lung with miliary brain and pulmonary metastases with echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase translocation treated with crizotinib: a case report.	2012-12	22999080
Isolated central nervous system progression on Crizotinib: an Achilles heel of non-small cell lung cancer with EML4-ALK translocation?	2012-12	22986231
Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.	2012-11-15	22266870
Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer.	2012-11-01	22488744
Targeted therapy for lung cancer.	2012-11	22932130
Treatment of ALK-positive non-small cell lung cancer.	2012-10	23020724
Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study.	2012-10	22954507
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall cell lung cancer.	2012-09-15	22282074
Identifying and targeting ROS1 gene fusions in non-small cell lung cancer.	2012-09-01	22919003
Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants.	2012-09-01	22912387
[Cavitating nodules in a 40-year-old non-smoking woman: a very particular tumour].	2012-09	22980554
Targeting ALK: a promising strategy for the treatment of non-small cell lung cancer, non-Hodgkin's lymphoma, and neuroblastoma.	2012-09	22968692
Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-targeted therapy for advanced non-small cell lung cancer: molecular and clinical aspects.	2012-08	22568572
The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma.	2012-07-10	22789543
Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells.	2012-07-01	22553343
Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification.	2012-07	22729845
Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia.	2012-07	22683780
Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer.	2012-07	22617245
Crizotinib (PF-02341066) reverses multidrug resistance in cancer cells by inhibiting the function of P-glycoprotein.	2012-07	22233293
A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK.	2012-06-29	22659414
[Management of crizotinib, a new individualized treatment].	2012-06-21	22713522
Remarkable tumor response to crizotinib in a 14-year-old girl with ALK-positive non-small-cell lung cancer.	2012-06-01	22508824
Crizotinib in the treatment of non-small-cell lung cancer.	2012-06	22594847
Development of treatment strategies for advanced neuroblastoma.	2012-06	22588779
ALK inhibitor crizotinib combined with intrathecal methotrexate treatment for non-small cell lung cancer with leptomeningeal carcinomatosis.	2012-05	22385925
Aberrant expression of the transcriptional factor Twist1 promotes invasiveness in ALK-positive anaplastic large cell lymphoma.	2012-04	22155737
ROS1 rearrangements define a unique molecular class of lung cancers.	2012-03-10	22215748
Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer.	2012-03-01	22235099
Pharmacokinetic/pharmacodynamic modeling of crizotinib for anaplastic lymphoma kinase inhibition and antitumor efficacy in human tumor xenograft mouse models.	2012-03	22129595
Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers.	2012-02-08	22277784
Rapid radiographic and clinical improvement after treatment of a MET-amplified recurrent glioblastoma with a mesenchymal-epithelial transition inhibitor.	2012-01-20	22162573
Personalized therapy of lung cancer.	2012	22286583
MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib.	2011-12-20	22042947
ALK mutations conferring differential resistance to structurally diverse ALK inhibitors.	2011-12-01	21948233
Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen.	2011-12	22034911
Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma.	2011-11-09	22072639
Comprehensive analysis of kinase inhibitor selectivity.	2011-10-30	22037378
Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis.	2011-10	21933749
Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and ALK gene abnormalities.	2011-05	21904575

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose and schedule for crizotinib is 250 mg orally, twice daily, with or without food.

Route of Administration: fVal

In Vitro Use Guide

PF-2341066 potently inhibited NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells (mean IC50 value of 24 nmol/L). In biochemical and cellular screens, PF-2341066 was shown to be selective for c-Met and ALK at pharmacologically relevant concentrations across a panel of >120 diverse kinases. PF-2341066 potently inhibited cell proliferation, which was associated with G(1)-S-phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells at IC50 values of approximately 30 nmol/L but not ALK-negative lymphoma cells.

Substance Class	Chemical Created by `admin` on `Tue Apr 01 16:25:48 GMT 2025` Edited by `admin` on `Tue Apr 01 16:25:48 GMT 2025`
Record UNII	FB99MH8KWZ
Record Status	`Validated (UNII)`
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Name

Type

Language

Crizotinib acetate

Common Name

English

2-Pyridinamine, 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-, acetate (1:1)

Preferred Name

English

[3-[[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]oxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-yl]amine monoacetate

Systematic Name

English

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

Systematic Name

English

2-Pyridinamine, 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-, monoacetate

Systematic Name

English

Code System Code Type Description

PUBCHEM

67175389

Created by admin on Tue Apr 01 16:25:48 GMT 2025 , Edited by admin on Tue Apr 01 16:25:48 GMT 2025

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FDA UNII

FB99MH8KWZ

Created by admin on Tue Apr 01 16:25:48 GMT 2025 , Edited by admin on Tue Apr 01 16:25:48 GMT 2025

PRIMARY

CAS

877399-53-6

Created by admin on Tue Apr 01 16:25:48 GMT 2025 , Edited by admin on Tue Apr 01 16:25:48 GMT 2025

PRIMARY

EPA CompTox

DTXSID00236600

Created by admin on Tue Apr 01 16:25:48 GMT 2025 , Edited by admin on Tue Apr 01 16:25:48 GMT 2025

PRIMARY

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ACTIVE MOIETY

Amount:

Details

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InChI

CNS Activity

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Cmax

AUC

T1/2

Funbound

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Overview

OverviewOther

Drug as perpetrator​

Drug as victim

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PubMed

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C_max

T_1/2

F_unbound

Drug as perpetrator