Identification

Name
Crizotinib
Accession Number
DB08865  (DB08700)
Type
Small Molecule
Groups
Approved
Description

Crizotinib an inhibitor of receptor tyrosine kinase for the treatment of non-small cell lung cancer (NSCLC). Verification of the presence of ALK fusion gene is done by Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit. This verification is used to select for patients suitable for treatment. FDA approved in August 26, 2011.

Structure
Thumb
Synonyms
  • (R)-crizotinib
  • Crizotinib
  • Crizotinibum
External IDs
1066 / PF 02341066 / PF 2341066 / PF-02341066 / PF-2341066
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
XalkoriCapsule200 mgOralPfizer2012-10-23Not applicableEu
XalkoriCapsule200 mgOralPfizer2012-05-10Not applicableCanada
XalkoriCapsule250 mgOralPfizer2012-10-23Not applicableEu
XalkoriCapsule200 mgOralPfizer2012-10-23Not applicableEu
XalkoriCapsule200 mg/1OralPfizer Laboratories Div Pfizer Inc.2011-08-26Not applicableUs
XalkoriCapsule250 mgOralPfizer2012-10-23Not applicableEu
XalkoriCapsule250 mgOralPfizer2012-05-10Not applicableCanada
XalkoriCapsule250 mg/1OralPfizer Laboratories Div Pfizer Inc.2011-08-26Not applicableUs
Categories
UNII
53AH36668S
CAS number
877399-52-5
Weight
Average: 450.337
Monoisotopic: 449.11854397
Chemical Formula
C21H22Cl2FN5O
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

Pharmacology

Indication

Crizotinib is used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic-lymphoma kinase (ALK)-positive as detected by a FDA-approved test.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Crizotinib is a tyrosine kinase receptor inhibitor. More specifically, it inhibits anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), and Recepteur d'Origine Nantais (RON). Abnormalities in the ALK gene caused by mutations or translocations may lead to expression of oncogenic fusion proteins. In patients with NSCLC, they have the EML4-ALK gene. Crizotinib inhibits ALK tyrosine kinase which ultimately results in decreased proliferation of cells that carry the genetic mutation and tumour survivability.

TargetActionsOrganism
AALK tyrosine kinase receptor
inhibitor
Human
AHepatocyte growth factor receptor
inhibitor
Human
Absorption

The peak serum concentration was reached in 4 to 6 hours following an oral single-dose administration. Steady state was reached within 15 days when a dose of 250 mg twice daily was administered. The mean absolute bioavailability was 43% (range of 32% to 66%) following a single 250 mg oral dose. When taken with high-fat meal, AUC and Cmax were reduced.

Volume of distribution

Mean volume of distribution (Vss) is 1772 L following intravenous administration of a 50 mg dose. This high volume of distribution suggest extensive distribution into tissue from plasma.

Protein binding

Crizotinib is 91% bound to plasma protein. This is not affected by drug concentration.

Metabolism

Crizotinib is metabolized by CYP3A4 and CYP3A5 in which these enzymes mediates the O-dealkylation of the drug.

Route of elimination

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

Half life

Plasma terminal half-life, patients = 42 hours

Clearance

The mean apparent clearance (CL/F) of crizotinib was lower at steady state (60 L/hr) after 250 mg twice daily than that after a single 250 mg oral dose (100 L/hr), which was likely due to autoinhibition of CYP3A by crizotinib after multiple dosing.

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Crizotinib.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Crizotinib.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Crizotinib.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Crizotinib.
AcetaminophenThe serum concentration of Crizotinib can be increased when it is combined with Acetaminophen.
Acetyl sulfisoxazoleThe metabolism of Crizotinib can be decreased when combined with Acetyl sulfisoxazole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Crizotinib.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Crizotinib.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Crizotinib.
AdinazolamThe metabolism of Adinazolam can be decreased when combined with Crizotinib.
Food Interactions
  • When given with a high-fat meal, AUC and Cmax were reduced by 14%. Despite this, crizotinib may be given with or without food.

References

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. [PubMed:23686600]
  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. [PubMed:22594847]
External Links
KEGG Drug
D09731
PubChem Compound
11626560
PubChem Substance
310264901
ChemSpider
9801307
BindingDB
50306682
ChEBI
64310
ChEMBL
CHEMBL601719
PharmGKB
PA165946122
HET
VGH
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Crizotinib
ATC Codes
L01XE16 — Crizotinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2wgj / 2xp2 / 2yfx / 3zbf / 4anq / 4ans / 4c9w / 5aaa / 5aab / 5aac
FDA label
Download (279 KB)
MSDS
Download (105 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1Active Not RecruitingTreatmentAdvanced Cancers3
1Active Not RecruitingTreatmentAdvanced Lung Cancer1
1Active Not RecruitingTreatmentAdvanced Solid Tumors1
1Active Not RecruitingTreatmentCastration-Resistant Prostate Cancer (CRPC)1
1Active Not RecruitingTreatmentDiffuse Intrinsic Pontine Glioma (DIPG) / High-Grade Gliomas1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1Active Not RecruitingTreatmentNeoplasms Malignant1
1Active Not RecruitingTreatmentRecurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Neuroblastoma / Unspecified Childhood Solid Tumor, Protocol Specific1
1CompletedNot AvailableHealthy Volunteers6
1CompletedBasic ScienceCancer, Advanced1
1CompletedBasic ScienceHealthy Volunteers6
1CompletedBasic ScienceImpaired Renal Function1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1RecruitingTreatmentALK-positive Advanced NSCLC1
1RecruitingTreatmentAdvanced Malignancies (Except Leukemia) / Advanced Malignancies Except Leukemia / Non-Small Cell Lung Cancer (ALK-positive) / Non-Small Cell Lung Cancer (c-Met Dependent) / Non-Small Cell Lung Cancer (ROS Marker Positive) / Non-Small Cell Lung Cancer ALK-positive / Non-Small Cell Lung Cancer c-Met Dependent / Non-Small Cell Lung Cancer ROS Marker Positive / Systemic Anaplastic Large-Cell Lymphoma1
1RecruitingTreatmentColorectal Cancers / Tumors, Solid1
1RecruitingTreatmentGlioblastoma Multiforme (Grade IV) of Cerebellum1
1TerminatedTreatmentAdenocarcinomas / Carcinoma, Large Cell / Non-Small Cell Lung Carcinoma (NSCLC) / Squamous Cell Carcinoma (SCC)1
1TerminatedTreatmentCancer, Breast1
1, 2Active Not RecruitingTreatmentBrain and Central Nervous System Tumors / Malignant Lymphomas / Neuroblastomas / Unspecified Childhood Solid Tumor, Protocol Specific1
1, 2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC1
2Active Not RecruitingTreatmentAdenocarcinomas / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
2Active Not RecruitingTreatmentCrizotinib / Lung Cancer Non-Small Cell Cancer (NSCLC) / ROS1 Proto Oncogene1
2Active Not RecruitingTreatmentHematologic Cancers / Metastatic Cancers / Tumors, Solid1
2Active Not RecruitingTreatmentLocally Advanced and/or Metastatic Alveolar Rhabdomyosarcoma / Locally Advanced and/or Metastatic Alveolar Soft Part Sarcoma / Locally Advanced and/or Metastatic Anaplastic Large Cell Lymphoma / Locally Advanced and/or Metastatic Clear Cell Sarcoma / Locally Advanced and/or Metastatic Inflammatory Myofibroblastic Tumor / Locally Advanced and/or Metastatic Papillary Renal Cell Carcinoma Type 11
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentUveal Melanoma1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentC-MET Positive Gastric Cancer1
2Not Yet RecruitingOtherLobular Breast Carcinoma / Malignant Neoplasm of Stomach1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentAdenocarcinomas / Lung Cancer Non-Small Cell Cancer (NSCLC) / Squamous Cell Carcinoma (SCC)1
2RecruitingTreatmentAdvanced Malignant Neoplasm / Advanced Malignant Solid Neoplasm / Bladder Carcinoma / Carcinoma, Breast / Carcinoma, Colorectal / Carcinoma, Pancreatic / Cervical Carcinoma / Colon Carcinoma / Endometrial Carcinoma / Gastric Carcinoma / Gliomas / Head and Neck Carcinoma / Liver and Intrahepatic Bile Duct Carcinoma / Lung, Carcinoma / Malignant Lymphomas / Malignant Uterine Neoplasm / Melanoma / Oesophageal Carcinoma / Ovarian Carcinoma / Plasma Cell Myeloma / Prostate Cancer / Rectal Carcinoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Cervical Carcinoma / Recurrent Colon Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gliomas / Recurrent Head and Neck Carcinoma / Recurrent Liver Carcinoma / Recurrent Lung Carcinoma / Recurrent Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Plasma Cell Myeloma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Solid Neoplasm / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Carcinoma / Refractory Lymphomas / Refractory Malignant Neoplasm / Refractory Malignant Solid Neoplasm / Refractory Plasma Cell Myeloma / Renal Carcinoma / Skin Carcinoma / Solid Neoplasms / Thyroid Gland Carcinoma / Uterine Corpus Cancer1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)2
2RecruitingTreatmentAnaplastic Large Cell Lymphoma, ALK-Positive / Ann Arbor Stage II Childhood Anaplastic Large Cell Lymphoma / Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma / Ann Arbor Stage III Childhood Anaplastic Large Cell Lymphoma / Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma / Ann Arbor Stage IV Childhood Anaplastic Large Cell Lymphoma / Ann Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma / CD30-Positive Neoplastic Cells Present / Stage II Childhood Anaplastic Large Cell Lymphoma / Stage III Childhood Anaplastic Large Cell Lymphoma / Stage IV Childhood Anaplastic Large Cell Lymphoma1
2RecruitingTreatmentAnaplastic Large Cell Lymphoma, ALK-Positive / Lymphoma ALK+1
2RecruitingTreatmentCholangiocarcinoma of the Extrahepatic Bile Duct / Gallbladder Cancer1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2RecruitingTreatmentNeuroblastomas1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2RecruitingTreatmentRenal Cell Carcinoma Recurrent / Stage III Renal Cell Cancer / Stage III Renal Cell Cancer AJCC v7 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V7 / Type 1 Papillary Renal Cell Carcinoma / Type 2 Papillary Renal Cell Carcinoma1
2RecruitingTreatmentUreteral Neoplasms / Urethral Neoplasms / Urinary Bladder Neoplasms1
2RecruitingTreatmentMetastatic Lung Adenocarcinoma1
2SuspendedTreatmentAdenocarcinoma of the Lung / Large Cell Lung Cancer / Non-Small Cell Lung Cancer Recurrent / Stage IV Non-Small Cell Lung Cancer1
2TerminatedTreatmentStage III Non-Small Cell Lung Cancer AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v71
2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Active Not RecruitingTreatmentAdvanced Malignancies / Carcinoma NOS / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
3Active Not RecruitingTreatmentAnaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer1
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3RecruitingScreeningAdenocarcinoma of the Lung / Adenosquamous Lung Carcinoma / Large Cell Lung Carcinoma / Stage IB Non-Small Cell Lung Carcinoma / Stage IB Non-Small Cell Lung Carcinoma AJCC v7 / Stage IB Squamous Cell Lung Carcinoma / Stage IB Squamous Cell Lung Carcinoma AJCC v7 / Stage II Non-Small Cell Lung Cancer / Stage II Non-Small Cell Lung Cancer AJCC v7 / Stage II Squamous Cell Lung Carcinoma / Stage II Squamous Cell Lung Carcinoma AJCC v7 / Stage IIA Non-Small Cell Lung Carcinoma / Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIA Squamous Cell Lung Carcinoma / Stage IIA Squamous Cell Lung Carcinoma AJCC v7 / Stage IIB Non-Small Cell Lung Carcinoma / Stage IIB Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIB Squamous Cell Lung Carcinoma / Stage IIB Squamous Cell Lung Carcinoma AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIA Squamous Cell Lung Carcinoma / Stage IIIA Squamous Cell Lung Carcinoma AJCC v71
3RecruitingTreatmentALK Gene Rearrangement / ALK Gene Translocation / ALK positive / Stage IB Non-Small Cell Lung Carcinoma / Stage IB Non-Small Cell Lung Carcinoma AJCC v7 / Stage II Non-Small Cell Lung Cancer AJCC v7 / Stage IIA Non-Small Cell Lung Carcinoma / Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIB Non-Small Cell Lung Carcinoma / Stage IIB Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v71
3RecruitingTreatmentChildhood Ganglioneuroblastoma / Childhood Neuroblastoma / INRG Stage L2 / INRG Stage M / INRG Stage MS / NMYC Gene Amplification / Recurrent Neuroblastoma1
3RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
3RecruitingTreatmentNeoplasms1
4Not Yet RecruitingTreatmentALK-positive NSCLC1
4WithdrawnTreatmentSystemic Anaplastic Large-Cell Lymphoma1
Not AvailableActive Not RecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableAvailableNot AvailableNeoplasms1
Not AvailableNo Longer AvailableNot AvailableInflammatory Myofibroblastic Tumors1
Not AvailableNo Longer AvailableNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms1
Not AvailableRecruitingNot AvailableEffectiveness and Safety for Real World Study on Crizotinib Used for ROS1 Arranged Non-squamous Non-small Cell Lung Cancer1
Not AvailableRecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral200 mg
CapsuleOral200 mg/1
CapsuleOral250 mg
CapsuleOral250 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2517256No2013-04-302024-02-26Canada
CA2577937No2010-12-212025-08-15Canada
CA2578066No2011-10-112025-08-15Canada
CA2632286No2011-11-152026-11-23Canada
US7825137No2007-05-122027-05-12Us
US7858643No2009-10-082029-10-08Us
US7230098No2005-08-262025-08-26Us
US8217057No2009-11-062029-11-06Us
US8785632No2005-03-012025-03-01Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.83 MSDS
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

Taxonomy

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
3-pyrazolylpyridine / 1,3-dichlorobenzene / Alkyl aryl ether / Aminopyridine / Halobenzene / Fluorobenzene / Chlorobenzene / Aryl chloride / Aryl fluoride / Aryl halide
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)

Targets

Kind
Protein
Organism
Human
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. [PubMed:22594847]
Kind
Protein
Organism
Human
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. [PubMed:22594847]
  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. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:23686600]
  2. Xalkori (Crizotinib) FDA Label [Link]
Kind
Protein
Organism
Human
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. [PubMed:23686600]
  2. Xalkori (Crizotinib) FDA Label [Link]
Kind
Protein
Organism
Human
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
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
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. [PubMed:24713129]

Transporters

Kind
Protein
Organism
Human
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. 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. [PubMed:23686600]

Drug created on March 28, 2013 11:22 / Updated on September 22, 2018 22:36