Identification

Summary

Crizotinib is a receptor tyrosine kinase inhibitor used to treat metastatic non-small cell lung cancer (NSCLC) where the tumors have been confirmed to be anaplastic lymphoma kinase (ALK), or ROS1-positive.

Brand Names
Xalkori
Generic Name
Crizotinib
DrugBank Accession Number
DB08865
Background

Crizotinib is a tyrosine kinase receptor inhibitor used for the treatment of anaplastic lymphoma kinase (ALK) or ROS1-positive non-small cell lung cancer (NSCLC) tumors, as well as ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT).4 By targeting the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein, crizotinib offers robust effectiveness in treating NSCLC in patients with this type of rearrangement.3 Crizotinib was the first-in-class drug used to treat ALK-positive tumors. Second- and third-generation ALK-tyrosine kinase-inhibitors have overcome many of the pharmacodynamic and genetic resistance mechanisms crizotinib is prone to.3 Crizotinib was approved by the FDA in 2011, and its use is accompanied by FDA-approved tests used to detect ALK and ROS1 rearrangements.4

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 450.337
Monoisotopic: 449.11854397
Chemical Formula
C21H22Cl2FN5O
Synonyms
  • (R)-crizotinib
  • Crizotinib
  • Crizotinibum
External IDs
  • 1066
  • PF 02341066
  • PF 2341066
  • PF-02341066
  • PF-2341066

Pharmacology

Indication

Crizotinib is a kinase inhibitor indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test.4 Crizotinib is also indicated for the treatment of relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive in pediatric patients 1 year of age and older and young adults. The safety and efficacy of crizotinib have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.4 Additionally, crizotinib is indicated for the treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.4

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

In a phase I study, 37 patients with a variety of solid-tumor cancers refractory to therapy received 50 to 300 mg of crizotinib daily or twice daily. In this group, two patients with non-small cell lung cancer (NSCLC) exhibiting echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) mutations responded to therapy; therefore, following studies focused on patients with advanced ALK-positive disease.1 In this group of patients, the 6-month progression-free survival among crizotinib users was approximately 72%. When compared to ALK mutation-positive patients that did not receive crizotinib, ALK mutation-positive patients treated with crizotinib had a higher two-year overall survival rate (54% vs 36%).1

The use of crizotinib may lead to hepatotoxicity, interstitial lung disease (ILD), pneumonitis, QT interval prolongation, bradycardia, severe visual loss, ​​embryo-fetal toxicity and gastrointestinal toxicity in pediatric and young adult patients with anaplastic large cell lymphoma (ALCL) or pediatric patients with inflammatory myofibroblastic tumor (IMT).4

Mechanism of action

Crizotinib is a tyrosine kinase receptor inhibitor that targets anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), ROS1 (c-ros), and Recepteur d'Origine Nantais (RON).4 When activated, ALK inhibits apoptosis and promotes cell proliferation, and ALK-gene translocations can lead to the expression of oncogenic fusion proteins. A small portion of non-small cell lung cancer (NSCLC) patients have ALK-positive tumors. Most of these cases are characterized by the fusion of ALK with the chimeric protein echinoderm microtubule-associated protein-like 4 (EML4), resulting in increased kinase activity.1,4 Crizotinib inhibits ALK by inhibiting its phosphorylation and creating an inactive protein conformation.3 This ultimately lowers the proliferation of cells carrying this genetic mutation and tumour survivability.4

In vitro assays on tumor cell lines demonstrated that crizotinib inhibits ALK, ROS1, and c-Met phosphorylation in a concentration-dependent manner. In vivo studies in mice with tumor xenografts that expressed EML4- or nucleophosmin (NPM)-ALK fusion proteins or c-Met showed that crizotinib has antitumor activity.4

TargetActionsOrganism
AALK tyrosine kinase receptor
inhibitor
Humans
AHepatocyte growth factor receptor
inhibitor
Humans
AProto-oncogene tyrosine-protein kinase ROS
inhibitor
Humans
AMacrophage-stimulating protein receptor
inhibitor
Humans
Absorption

In patients with pancreatic, colorectal, sarcoma, anaplastic large-cell lymphoma and non-small cell lung cancer (NSCLC) treated with crizotinib doses ranging from 100 mg once a day to 300 mg twice a day, the mean AUC and Cmax increased in a dose-proportional manner.2 A single crizotinib dose of crizotinib is absorbed with a median tmax 4 to 6 hours.4 In patients receiving multiple doses of crizotinib 250 mg twice daily (n=167), the mean AUC was is 2321.00 ng⋅hr/mL, the mean Cmax was 99.60 ng/mL, and the median tmax was 5.0 hours.1 The mean absolute bioavailability of crizotinib is 43%, ranging from 32% to 66%. High-fat meals reduce the AUC0-INF and Cmax of crizotinib by approximately 14%.4 Age, sex at birth, and ethnicity (Asian vs non-Asian patients) did not have a clinically significant effect on crizotinib pharmacokinetics. In patients less than 18 years old, higher body weight was associated with a lower crizotinib exposure.4

Volume of distribution

Following a single intravenous dose, the mean volume of distribution (Vss) of crizotinib was 1772 L.4

Protein binding

Crizotinib is 91% bound to plasma protein. In vitro studies suggest that this is not affected by drug concentration.4

Metabolism

Crizotinib is mainly metabolized in the liver by CYP3A4 and CYP3A5, and undergoes an O-dealkylation, with subsequent phase 2 conjugation.1 Non-metabolic elimination, such as biliary excretion, can not be excluded.5 PF-06260182 (with two constituent diastereomers, PF-06270079 and PF-06270080) is the only active metabolite of crizotinib that has been identified. In vitro studies suggest that, compared to crizotinib, PF-06270079 and PF-06270080 are approximately 3- to 8-fold less potent against anaplastic lymphoma kinase (ALK) and 2.5- to 4-fold less potent against Hepatocyte Growth Factor Receptor (HGFR, c-Met).5

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Route of elimination

After administering a single 250 mg radiolabeled crizotinib dose to healthy subjects, 63% and 22% of the administered dose were recovered in feces and urine. Unchanged crizotinib represented approximately 53% and 2.3% of the administered dose in feces and urine, respectively.4

Half-life

Following single doses of crizotinib, the plasma terminal half-life was 42 hours.4

Clearance

At steady-state (250 mg twice daily), crizotinib has a mean apparent clearance (CL/F) of 60 L/hr. This value is lower than the one detected after a single 250 mg oral dose (100 L/hr),4, possibly due to CYP3A auto-inhibition.5

Adverse Effects
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Toxicity

The maximum tolerated dose of crizotinib is the same as the recommended dosing regimen (250 mg twice daily). This was defined based on a phase 1 dose-escalation study in patients with advanced solid tumors. The treatment of crizotinib overdoses should consist of symptomatic treatment and other supportive measures. There is no antidote for crizotinib.6 In vitro and in vivo studies have shown that crizotinib is genotoxic, and the Ames test showed that crizotinib was not mutagenic. Carcinogenicity studies with crizotinib have not been performed.4

In female rats, 500 mg/kg/day (approximately 10 times the recommended human dose based on body surface area) of crizotinib for 3 days induced single-cell necrosis of ovarian follicles. In male rats, 50 mg/kg/day of crizotinib (greater than 1.7 times the recommended human dose) for 28 days induced testicular pachytene spermatocyte degeneration.4

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Crizotinib.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Crizotinib.
AbametapirThe serum concentration of Crizotinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Crizotinib can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Crizotinib.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Crizotinib.
AbrocitinibThe serum concentration of Crizotinib can be increased when it is combined with Abrocitinib.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Crizotinib.
AcebutololCrizotinib may increase the bradycardic activities of Acebutolol.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Crizotinib.
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Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum levels of crizotinib.
  • Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of crizotinib.
  • Take with or without food. High-fat food decreases drug absorption, but not to a clinically significant extent.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
XalkoriCapsule200 mgOralPfizer Europe Ma Eeig2016-09-08Not applicableEU flag
XalkoriCapsule250 mgOralPfizer Canada Ulc2012-05-10Not applicableCanada flag
XalkoriCapsule250 mg/1OralPfizer Laboratories Div Pfizer Inc2011-08-26Not applicableUS flag
XalkoriCapsule250 mgOralPfizer Europe Ma Eeig2016-09-08Not applicableEU flag
XalkoriCapsule200 mgOralPfizer Canada Ulc2012-05-10Not applicableCanada flag
XalkoriCapsule200 mgOralPfizer Europe Ma Eeig2016-09-08Not applicableEU flag
XalkoriCapsule250 mgOralPfizer Europe Ma Eeig2016-09-08Not applicableEU flag
XalkoriCapsule200 mg/1OralPfizer Laboratories Div Pfizer Inc2011-08-26Not applicableUS flag

Categories

ATC Codes
L01XE16 — Crizotinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrazolylpyridines. These are compounds containing a pyrazolylpyridine skeleton, which consists of a pyrazole linked (not fused) to a pyridine by a bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pyrazolylpyridines
Direct Parent
Pyrazolylpyridines
Alternative Parents
Dichlorobenzenes / Alkyl aryl ethers / Aminopyridines and derivatives / Fluorobenzenes / Piperidines / Aryl chlorides / Aryl fluorides / Imidolactams / Pyrazoles / Heteroaromatic compounds
show 7 more
Substituents
1,3-dichlorobenzene / 3-pyrazolylpyridine / Alkyl aryl ether / Amine / Aminopyridine / Aromatic heteromonocyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine (CHEBI:64310)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
53AH36668S
CAS number
877399-52-5
InChI Key
KTEIFNKAUNYNJU-GFCCVEGCSA-N
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
IUPAC Name
3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine
SMILES
C[C@@H](OC1=CC(=CN=C1N)C1=CN(N=C1)C1CCNCC1)C1=C(Cl)C=CC(F)=C1Cl

References

Synthesis Reference

Cui, JJ., et al. (2014). Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors (U.S. Patent No. US 8,785,632 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/d5/82/7a/7fec499c2af772/US8785632.pdf

General References
  1. Timm A, Kolesar JM: Crizotinib for the treatment of non-small-cell lung cancer. Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7. doi: 10.2146/ajhp120261. [Article]
  2. Forde PM, Rudin CM: Crizotinib in the treatment of non-small-cell lung cancer. Expert Opin Pharmacother. 2012 Jun;13(8):1195-201. doi: 10.1517/14656566.2012.688029. [Article]
  3. Heigener DF, Reck M: Crizotinib. Recent Results Cancer Res. 2018;211:57-65. doi: 10.1007/978-3-319-91442-8_4. [Article]
  4. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
  5. FDA Clinical Pharmacology and Biopharmaceutics Review: XALKORI (crizotinib) capsules for oral use [Link]
  6. Health Canada Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
KEGG Drug
D09731
PubChem Compound
11626560
PubChem Substance
310264901
ChemSpider
9801307
BindingDB
50306682
RxNav
1148495
ChEBI
64310
ChEMBL
CHEMBL601719
ZINC
ZINC000035902489
PharmGKB
PA165946122
PDBe Ligand
VGH
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Crizotinib
PDB Entries
2wgj / 2xp2 / 2yfx / 3zbf / 4anq / 4ans / 4c9w / 5aaa / 5aab / 5aac
show 1 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentALK or ROS1-positive NSCLC1
4RecruitingTreatmentALCL / IMT / Non-Small Cell Lung Carcinoma (NSCLC)1
4RecruitingTreatmentAnaplastic Large Cell Lymphoma, ALK-Positive1
4WithdrawnTreatmentSystemic Anaplastic Large Cell Lymphoma1
3Active Not RecruitingTreatmentAnaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer1
3Active Not RecruitingTreatmentNeoplastic Disease1
3Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)3
3CompletedTreatmentAdvanced Malignancies / Carcinoma / Lung Cancers / Non-Small Cell Lung Carcinoma (NSCLC)1
3CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
3Not Yet RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral200 mg/1
CapsuleOral250 mg/1
Capsule, coatedOral200 mg
Capsule, coatedOral250 mg
CapsuleOral200 mg
CapsuleOral250 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2517256No2013-04-302024-02-26Canada flag
CA2577937No2010-12-212025-08-15Canada flag
CA2578066No2011-10-112025-08-15Canada flag
CA2632286No2011-11-152026-11-23Canada flag
US7825137No2010-11-022027-05-12US flag
US7858643No2010-12-282029-10-08US flag
US7230098No2007-06-122025-08-26US flag
US8217057No2012-07-102029-11-06US flag
US8785632No2014-07-222025-03-01US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleFDA Chemistry Review: XALKORI (crizotinib) Capsules. Available at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ChemR.pdf
logP1.83 EMA Assessment Report: XALKORI (crizotinib) Capsules. Available at https://www.ema.europa.eu/en/documents/variation-report/xalkori-h-c-2489-ii-0039-epar-assessment-report-variation_en.pdf
pKa9.4 and 5.6FDA Chemistry Review: XALKORI (crizotinib) Capsules. Available at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202570Orig1s000ChemR.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.00611 mg/mLALOGPS
logP3.82ALOGPS
logP3.57ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)10.12ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area77.99 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity128.43 m3·mol-1ChemAxon
Polarizability45.44 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9721
Caco-2 permeable-0.5672
P-glycoprotein substrateSubstrate0.6938
P-glycoprotein inhibitor INon-inhibitor0.6713
P-glycoprotein inhibitor IIInhibitor0.7105
Renal organic cation transporterInhibitor0.5464
CYP450 2C9 substrateNon-substrate0.7545
CYP450 2D6 substrateNon-substrate0.7023
CYP450 3A4 substrateSubstrate0.6029
CYP450 1A2 substrateInhibitor0.6676
CYP450 2C9 inhibitorInhibitor0.5
CYP450 2D6 inhibitorNon-inhibitor0.8662
CYP450 2C19 inhibitorInhibitor0.6237
CYP450 3A4 inhibitorNon-inhibitor0.6301
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8676
Ames testNon AMES toxic0.5981
CarcinogenicityNon-carcinogens0.8018
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6581 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.643
hERG inhibition (predictor II)Inhibitor0.7877
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-1693800000-fc52c38f3359a378554a

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis a...
Gene Name
ALK
Uniprot ID
Q9UM73
Uniprot Name
ALK tyrosine kinase receptor
Molecular Weight
176440.535 Da
References
  1. Forde PM, Rudin CM: Crizotinib in the treatment of non-small-cell lung cancer. Expert Opin Pharmacother. 2012 Jun;13(8):1195-201. doi: 10.1517/14656566.2012.688029. [Article]
  2. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
Gene Name
MET
Uniprot ID
P08581
Uniprot Name
Hepatocyte growth factor receptor
Molecular Weight
155540.035 Da
References
  1. Forde PM, Rudin CM: Crizotinib in the treatment of non-small-cell lung cancer. Expert Opin Pharmacother. 2012 Jun;13(8):1195-201. doi: 10.1517/14656566.2012.688029. [Article]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
  3. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.
Specific Function
Atp binding
Gene Name
ROS1
Uniprot ID
P08922
Uniprot Name
Proto-oncogene tyrosine-protein kinase ROS
Molecular Weight
263912.88 Da
References
  1. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand.
Specific Function
Atp binding
Gene Name
MST1R
Uniprot ID
Q04912
Uniprot Name
Macrophage-stimulating protein receptor
Molecular Weight
152240.095 Da
References
  1. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Timm A, Kolesar JM: Crizotinib for the treatment of non-small-cell lung cancer. Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7. doi: 10.2146/ajhp120261. [Article]
  2. Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [Article]
  3. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Timm A, Kolesar JM: Crizotinib for the treatment of non-small-cell lung cancer. Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7. doi: 10.2146/ajhp120261. [Article]
  2. Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [Article]
  3. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:
References
  1. Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [Article]
  2. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Clinical Pharmacology and Biopharmaceutics Review: XALKORI (crizotinib) capsules for oral use [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
References
  1. FDA Clinical Pharmacology and Biopharmaceutics Review: XALKORI (crizotinib) capsules for oral use [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Zhou WJ, Zhang X, Cheng C, Wang F, Wang XK, Liang YJ, To KK, Zhou W, Huang HB, Fu LW: Crizotinib (PF-02341066) reverses multidrug resistance in cancer cells by inhibiting the function of P-glycoprotein. Br J Pharmacol. 2012 Jul;166(5):1669-83. doi: 10.1111/j.1476-5381.2012.01849.x. [Article]
  2. FDA Approved Drug Products: XALKORI (crizotinib) capsules for oral use [Link]

Drug created at March 28, 2013 17:22 / Updated at August 19, 2022 08:38