Crizotinib hydrochloride

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H22Cl2FN5O.ClH
Molecular Weight	486.798
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=BTDNHKQCPIBABF-UTONKHPSSA-N

InChI=1S/C21H22Cl2FN5O.ClH/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);1H/t12-;/m1./s1

HIDE SMILES / InChI

Description
Sources: http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm376058.htm?source=govdelivery&utm_medium=email&utm_source=govdeliveryhttps://www.ncbi.nlm.nih.gov/pubmed/24695225
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

(S)-crizotinib was discovered as an attractive chemical entity for further pre-clinical evaluation, and small-molecule inhibitors of MTH1 as a promising novel class of anticancer agents.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
ALK tyrosine kinase receptor 25 Target ID: CHEMBL4247 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202570s006lbl.pdf	Inhibitor 8297	24.0 nM [IC50]
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202570s006lbl.pdf	Inhibitor 8297	11.0 nM [IC50]
7,8-dihydro-8-oxoguanine triphosphatase 4 Target ID: P36639 Gene ID: 4521.0 Gene Symbol: NUDT1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24695225	Inhibitor 8297	72.0 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 8429	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
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24695225	Primary		Basic research	Unknown Approved Use Unknown

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
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
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 unknown	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 unknown	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 unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

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
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
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 unknown	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 unknown	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 unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
47.1 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 unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

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 n = 6 Health Status: unhealthy Age Group: 49 years Sex: M+F Population Size: 6 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) n = 119 Health Status: unhealthy Condition: Adenocarcinoma \| Squamous Cell Carcinoma \|Non-small Cell Lung Cancer Age Group: 51 years (range: 21-79 years) Sex: M+F Population Size: 119 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) n = 136 Health Status: unhealthy Condition: Adenocarcinoma \| Adenosquamous Carcinoma\|Non-small Cell Lung Cancer Age Group: 52 years (range: 29-82 years) Sex: M+F Population Size: 136 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 n = 6 Health Status: unhealthy Age Group: 49 years Sex: M+F Population Size: 6 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) n = 119 Health Status: unhealthy Condition: Adenocarcinoma \| Squamous Cell Carcinoma \|Non-small Cell Lung Cancer Age Group: 51 years (range: 21-79 years) Sex: M+F Population Size: 119 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) n = 136 Health Status: unhealthy Condition: Adenocarcinoma \| Adenosquamous Carcinoma\|Non-small Cell Lung Cancer Age Group: 52 years (range: 29-82 years) Sex: M+F Population Size: 136 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) n = 136 Health Status: unhealthy Condition: Adenocarcinoma \| Adenosquamous Carcinoma\|Non-small Cell Lung Cancer Age Group: 52 years (range: 29-82 years) Sex: M+F Population Size: 136 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 214 P-gp 1461 CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 OATP1B1 788 OATP1B3 706 BCRP 699 Ca2+ channels 57 L-type Ca2+ channels 28 Nav1.5 97	CYP3A5 395 CYP2C19 991 CYP2C8 693 CYP1A2 1054 P-gp 1537	CYP3A 129 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	weak [IC50 44 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	weak [IC50 48 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	weak [Inhibition 30 uM]
Ca2+ channels 60	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf	yes [IC50 0.83 uM]
L-type Ca2+ channels 30	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf	yes [IC50 14.6 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 22 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 23 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 5.79 uM]
CYP3A 298	inhibitor 3277 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 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes [IC50 >30 uM]
CYP3A4 1925	inducer 1573 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 1737	substrate 3367 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 395	substrate 3367 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 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	minor
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	minor
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ClinPharmR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 100	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000PharmR.pdf
hERG 1647	inhibitor 1626 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
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
eMolecules	31526065	https://www.emolecules.com/cgi-bin/more?vid=31526065

PubMed

Title	Date	PubMed
		252160340
Rapid and dramatic radiographic and clinical response to an ALK inhibitor (crizotinib, PF02341066) in an ALK translocation-positive patient with non-small cell lung cancer.	2010 Dec	21102269
New drugs in advanced non-small-cell lung cancer: searching for the correct clinical development.	2010 Dec	21047279
ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time.	2010 Dec 14	21156280
Deciding priorities in Pharma.	2010 Dec 20	21172084
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Favorable response to crizotinib in three patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion-type oncogene-positive non-small cell lung cancer.	2011 Aug	21767331
Differential (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine PET responses to pharmacologic inhibition of the c-MET receptor in preclinical tumor models.	2011 Aug	21764800
Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen.	2011 Dec	22034911
Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification.	2011 May	21623265
Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK.	2011 May 3	21502504
Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma.	2011 Nov 9	22072639
Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis.	2011 Oct	21933749
MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in non-small cell lung cancer according to MET alterations.	2011 Oct	21716144
Personalized therapy of lung cancer.	2012	22286583
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 Dec	22999080
Isolated central nervous system progression on Crizotinib: an Achilles heel of non-small cell lung cancer with EML4-ALK translocation?	2012 Dec	22986231
Anaplastic Lymphoma Kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells.	2012 Dec 13	22286764
Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers.	2012 Feb 8	22277784
ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity.	2012 Jan	21757253
Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification.	2012 Jul	22729845
Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia.	2012 Jul	22683780
Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer.	2012 Jul	22617245
The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma.	2012 Jul 10	22789543
[Management of crizotinib, a new individualized treatment].	2012 Jul-Aug	22713522
Development of treatment strategies for advanced neuroblastoma.	2012 Jun	22588779
Remarkable tumor response to crizotinib in a 14-year-old girl with ALK-positive non-small-cell lung cancer.	2012 Jun 1	22508824
A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK.	2012 Jun 29	22659414
Pharmacokinetic/pharmacodynamic modeling of crizotinib for anaplastic lymphoma kinase inhibition and antitumor efficacy in human tumor xenograft mouse models.	2012 Mar	22129595
ROS1 rearrangements define a unique molecular class of lung cancers.	2012 Mar 10	22215748
ALK inhibitor crizotinib combined with intrathecal methotrexate treatment for non-small cell lung cancer with leptomeningeal carcinomatosis.	2012 May	22385925
Targeted therapy for lung cancer.	2012 Nov	22932130
Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer.	2012 Nov 1	22488744
Antibody targeting of anaplastic lymphoma kinase induces cytotoxicity of human neuroblastoma.	2012 Nov 15	22266870
Treatment of ALK-positive non-small cell lung cancer.	2012 Oct	23020724
Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study.	2012 Oct	22954507
[Cavitating nodules in a 40-year-old non-smoking woman: a very particular tumour].	2012 Sep	22980554
Targeting ALK: a promising strategy for the treatment of non-small cell lung cancer, non-Hodgkin's lymphoma, and neuroblastoma.	2012 Sep	22968692
Identifying and targeting ROS1 gene fusions in non-small cell lung cancer.	2012 Sep 1	22919003
Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants.	2012 Sep 1	22912387
Enhancement of the antiproliferative activity of gemcitabine by modulation of c-Met pathway in pancreatic cancer.	2013	22973962
Development and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors.	2013 Apr	23134735
Prediction of crizotinib-midazolam interaction using the Simcyp population-based simulator: comparison of CYP3A time-dependent inhibition between human liver microsomes versus hepatocytes.	2013 Feb	23129213
Overcoming erlotinib resistance with tailored treatment regimen in patient-derived xenografts from naïve Asian NSCLC patients.	2013 Jan 15	22948846
Crizotinib for the treatment of non-small-cell lung cancer.	2013 Jun 1	23686600
Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.	2013 Mar	23104988
Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC).	2013 May	22703830
Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes.	2013 Oct 1	23707608
Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy.	2014 Apr 10	24695225
Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.	2015 Jan 5	25569083

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.

Name

Type

Language

Crizotinib hydrochloride

Common Name

English

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

Systematic 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 hydrochloride

Systematic Name

English

Code System Code Type Description

FDA UNII

Z63P44CE4Z

Created by admin on Sat Dec 16 20:18:38 GMT 2023 , Edited by admin on Sat Dec 16 20:18:38 GMT 2023

PRIMARY

CAS

1415560-69-8

Created by admin on Sat Dec 16 20:18:38 GMT 2023 , Edited by admin on Sat Dec 16 20:18:38 GMT 2023

PRIMARY

PUBCHEM

71576688

Created by admin on Sat Dec 16 20:18:38 GMT 2023 , Edited by admin on Sat Dec 16 20:18:38 GMT 2023

PRIMARY

ACTIVE MOIETY


					53AH36668S

Crizotinib

SUBSTANCE RECORD


					Z63P44CE4Z

Crizotinib hydrochloride

Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator