DGIdb - CRIZOTINIB Drug Record

CRIZOTINIB chembl:CHEMBL601719 ApprovedAntineoplastic

Alternate Names:

PF-02341066
XALKORI
CRIZOTINIB
PF-2341066
XALKORI®
PF2341066
(R)-CRIZOTINIB
PF 2341066
chembl:CHEMBL601719
rxcui:1148495
drugbank:08700
chemidplus:877399-52-5
pubchem.compound:11626560

Drug Info:

Pharmaceutical Developer	Pfizer
Source Reported Drug Name(s)	Crizotinib/Xalkori/PF-02341066
Drug Class	ALK Inhibitor
FDA Approval	approved
Drug Class	Small molecule
Drug Indications	antineoplastic agent
FDA Approval	Non-small cell lung cancer (with ALK fusion or ROS1 gene alteration)
Drug Class	Kinase Inhibitors
Drug Categories	amines
Drug Categories	aminopyridines
Drug Categories	cytochrome p-450 cyp2b6 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 inhibitors
Drug Categories	cytochrome p-450 cyp3a4 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 cyp3a5 inhibitors
Drug Categories	cytochrome p-450 cyp3a5 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp3a5 substrates
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 substrates
Drug Categories	kinase inhibitor
Drug Categories	oct2 inhibitors
Drug Categories	organic cation transporter 1 inhibitors
Drug Categories	p-glycoprotein inhibitors
Drug Categories	p-glycoprotein substrates
Drug Categories	p-glycoprotein substrates with narrow therapeutic index
Drug Categories	piperidines
Drug Categories	pyridines
Drug Categories	qtc prolonging agents
Drug Categories	receptor tyrosine kinase inhibitors
Drug Categories	tyrosine kinase inhibitors

(16 More Sources)

Publications:

Christensen et al., 2007, Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma., Mol. Cancer Ther.
Amin et al., 2016, TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors., Oncotarget
Zdzalik et al., 2014, Activating mutations in ALK kinase domain confer resistance to structurally unrelated ALK inhibitors in NPM-ALK-positive anaplastic large-cell lymphoma., J. Cancer Res. Clin. Oncol.
Mologni et al., 2015, NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922., Oncotarget
Ceccon et al., 2015, Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma., Mol. Cancer Res.
Katayama et al., 2014, Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib., Clin. Cancer Res.
Katayama et al., 2012, Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers., Sci Transl Med
Godbert et al., 2015, Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase-Rearranged Anaplastic Thyroid Carcinoma., J. Clin. Oncol.
Butrynski et al., 2010, Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor., N. Engl. J. Med.
Orimo et al., 1990, [The role of hyperlipidemia in the development of atherosclerosis]., Nippon Rinsho
Gambacorti Passerini et al., 2014, Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients., J. Natl. Cancer Inst.
Kanaan Z et al., 2015, Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond., Onco Targets Ther
Pall G, 2015, The next-generation ALK inhibitors., Curr Opin Oncol
Ehmann F et al., 2014, European Medicines Agency initiatives and perspectives on pharmacogenomics., Br J Clin Pharmacol
Sasaki et al., 2011, A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors., Cancer Res.
Heuckmann et al., 2011, ALK mutations conferring differential resistance to structurally diverse ALK inhibitors., Clin. Cancer Res.
Sasaki et al., 2010, The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers., Cancer Res.
Mossé et al., 2008, Identification of ALK as a major familial neuroblastoma predisposition gene., Nature
Sakamoto et al., 2011, CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant., Cancer Cell
Choi et al., 2010, EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors., N. Engl. J. Med.
Chen et al., 2014, Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance., Clin. Cancer Res.
Shaw et al., 2014, Ceritinib in ALK-rearranged non-small-cell lung cancer., N. Engl. J. Med.
Kim et al., 2013, Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer., J Thorac Oncol
Doebele et al., 2012, Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer., Clin. Cancer Res.
Janoueix-Lerosey et al., 2008, Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma., Nature
Mazot et al., 2011, The constitutive activity of the ALK mutated at positions F1174 or R1275 impairs receptor trafficking., Oncogene
Mossé et al., 2013, Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study., Lancet Oncol.
Schönherr et al., 2011, Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684., Biochem. J.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
George et al., 2008, Activating mutations in ALK provide a therapeutic target in neuroblastoma., Nature
Bresler et al., 2011, Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma., Sci Transl Med
Infarinato et al., 2016, The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma., Cancer Discov
Tardy S et al., 2014, Synthesis and biological evaluation of benzo[4,5]imidazo[1,2-c]pyrimidine and benzo[4,5]imidazo[1,2-a]pyrazine derivatives as anaplastic lymphoma kinase inhibitors., Bioorg Med Chem
Gambacorti-Passerini et al., 2011, Crizotinib in anaplastic large-cell lymphoma., N. Engl. J. Med.
Solomon et al., 2016, Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014., J. Clin. Oncol.
Ou et al., 2014, Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC., Ann. Oncol.
Solomon et al., 2014, First-line crizotinib versus chemotherapy in ALK-positive lung cancer., N. Engl. J. Med.
Shaw et al., 2013, Crizotinib versus chemotherapy in advanced ALK-positive lung cancer., N. Engl. J. Med.
Friboulet et al., 2014, The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer., Cancer Discov
Wiesner et al., 2015, Alternative transcription initiation leads to expression of a novel ALK isoform in cancer., Nature
Shaw et al., 2016, Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F., N. Engl. J. Med.
Kwak et al., 2010, Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer., N. Engl. J. Med.
Normant et al., 2011, The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models., Oncogene
Li et al., 2015, Promising response of anaplastic lymphoma kinase-positive large B-cell lymphoma to crizotinib salvage treatment: case report and review of literature., Int J Clin Exp Med
Chung et al., 2014, A Poorly Differentiated Malignant Neoplasm Lacking Lung Markers Harbors an EML4-ALK Rearrangement and Responds to Crizotinib., Case Rep Oncol
Peters et al., 2017, Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer., N. Engl. J. Med.
Le et al., 2015, Detection of Crizotinib-Sensitive Lung Adenocarcinomas With MET, ALK, and ROS1 Genomic Alterations via Comprehensive Genomic Profiling., Clin Lung Cancer
2015, Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer., N. Engl. J. Med.
Shaw et al., 2011, Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis., Lancet Oncol.
Forde et al., 2012, Crizotinib in the treatment of non-small-cell lung cancer., Expert Opin Pharmacother
Mossé et al., 2017, Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study., J. Clin. Oncol.
Malik et al., 2014, U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive., Clin. Cancer Res.
Lovly et al., 2011, Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors., Cancer Res.
Kodityal et al., 2016, A novel acquired ALK F1245C mutation confers resistance to crizotinib in ALK-positive NSCLC but is sensitive to ceritinib., Lung Cancer
Gainor et al., 2015, Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib., Clin. Cancer Res.
Morán et al., 2013, Targeting EML4-ALK driven non-small cell lung cancer (NSCLC)., Transl Lung Cancer Res
Krytska et al., 2016, Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma., Clin. Cancer Res.
Zhang et al., 2016, The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models., Clin. Cancer Res.
Gainor et al., 2016, Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer., Cancer Discov
Yoda S et al., 2018, Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound <i>ALK</i> Mutations in ALK-Positive Lung Cancer., Cancer Discov
Torossian A et al., 2019, Blockade of crizotinib-induced BCL2 elevation in ALK-positive anaplastic large cell lymphoma triggers autophagy associated with cell death., Haematologica
Foyil et al., Brentuximab vedotin and crizotinib in anaplastic large-cell lymphoma., Cancer J
Ceccon M et al., 2013, Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors., Mol Cancer Res
Lin H et al., 2018, A Novel EML6-ALK FBXO11-ALK Double Fusion Variant in Lung Adenocarcinoma and Response to Crizotinib., J Thorac Oncol
Le Rhun E et al., 2015, Patterns of response to crizotinib in recurrent glioblastoma according to ALK and MET molecular profile in two patients., CNS Oncol
Singhi et al., 2017, Identification of Targetable ALK Rearrangements in Pancreatic Ductal Adenocarcinoma., J Natl Compr Canc Netw
Katayama et al., 2015, Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer., Clin. Cancer Res.
Awad et al., 2013, Acquired resistance to crizotinib from a mutation in CD74-ROS1., N. Engl. J. Med.
Davare et al., 2015, Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors., Proc. Natl. Acad. Sci. U.S.A.
Song et al., 2015, Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer., Clin. Cancer Res.
Zou et al., 2015, PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations., Proc. Natl. Acad. Sci. U.S.A.
Mazières et al., 2015, Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort., J. Clin. Oncol.
Shaw et al., 2014, Crizotinib in ROS1-rearranged non-small-cell lung cancer., N. Engl. J. Med.
Lovly et al., 2014, Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions., Cancer Discov
Wu YL et al., 2018, Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer., J Clin Oncol
Bergethon et al., 2012, ROS1 rearrangements define a unique molecular class of lung cancers., J. Clin. Oncol.
Gainor JF et al., 2017, Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in <i>ROS1</i>-Positive Non-Small-Cell Lung Cancer., JCO Precis Oncol
Shaw AT et al., 2019, Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001., Ann Oncol
Lorenzato et al., 2002, Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion., Cancer Res.
Maulik et al., 2002, Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition., Cytokine Growth Factor Rev.
Bardelli et al., 1998, Uncoupling signal transducers from oncogenic MET mutants abrogates cell transformation and inhibits invasive growth., Proc. Natl. Acad. Sci. U.S.A.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Olivero et al., 1999, Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family., Int. J. Cancer
Dalinka et al., 1975, The radiology of osseous and articular infection., CRC Crit Rev Clin Radiol Nucl Med
Zou et al., 2007, An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms., Cancer Res.
Chu LP et al., 2019, MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel <i>MET</i> R1004G Mutation., Oncologist
Frampton et al., 2015, Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors., Cancer Discov
Awad et al., 2016, MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression., J. Clin. Oncol.
Paik et al., 2015, Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping., Cancer Discov
Togashi et al., 2015, MET gene exon 14 deletion created using the CRISPR/Cas9 system enhances cellular growth and sensitivity to a MET inhibitor., Lung Cancer
Bardelli et al., 2013, Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer., Cancer Discov
Palma et al., 2014, Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary., Case Rep Oncol
Pietrantonio et al., 2016, MET-Driven Resistance to Dual EGFR and BRAF Blockade May Be Overcome by Switching from EGFR to MET Inhibition in BRAF-Mutated Colorectal Cancer., Cancer Discov
Tanizaki et al., 2011, MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in non-small cell lung cancer according to MET alterations., J Thorac Oncol
Chi et al., 2012, Rapid radiographic and clinical improvement after treatment of a MET-amplified recurrent glioblastoma with a mesenchymal-epithelial transition inhibitor., J. Clin. Oncol.
Ou et al., 2011, 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., J Thorac Oncol
Ou SH, 2011, Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond., Drug Des Devel Ther
Li et al., 2017, Acquired MET Y1248H and D1246N Mutations Mediate Resistance to MET Inhibitors in Non-Small Cell Lung Cancer., Clin. Cancer Res.
Zick et al., 2017, Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients., Medicine (Baltimore)
Choi et al., 2004, Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines: less involvement of metallothionein., Cancer Cell Int.
Du et al., 2016, Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors., Nat. Med.
Qi et al., 2011, Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors., Cancer Res.
Kwak et al., 2015, Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer., Cancer Discov
Shen et al., 2015, c-Myc alterations confer therapeutic response and acquired resistance to c-Met inhibitors in MET-addicted cancers., Cancer Res.
Ou et al., 2016, High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression., Lung Cancer
Pfefferle et al., 2016, Genomic profiling of murine mammary tumors identifies potential personalized drug targets for p53-deficient mammary cancers., Dis Model Mech
Chabon et al., 2016, Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients., Nat Commun
Secrier et al., 2016, Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance., Nat. Genet.
Bahcall et al., 2016, Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer., Cancer Discov
Heist et al., 2016, Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping., J Thorac Oncol
Engstrom et al., 2017, Glesatinib Exhibits Antitumor Activity in Lung Cancer Models and Patients Harboring MET Exon 14 Mutations and Overcomes Mutation-Mediated Resistance to Type I MET Inhibitors in Nonclinical Models., Clin. Cancer Res.
Lu et al., 2017, MET Exon 14 Mutation Encodes an Actionable Therapeutic Target in Lung Adenocarcinoma., Cancer Res.
Moro-Sibilot D et al., 2019, Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial., Ann Oncol
Landi L et al., 2019, Crizotinib in <i>MET</i>-Deregulated or <i>ROS1</i>-Rearranged Pretreated Non-Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial., Clin Cancer Res
Mahjoubi L et al., 2016, A never-smoker lung adenocarcinoma patient with a MET exon 14 mutation (D1028N) and a rapid partial response after crizotinib., Invest New Drugs
Drilon A et al., 2020, Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration., Nat Med
Wiesweg M et al., 2020, Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation., Lung Cancer
Zhu YC et al., 2018, Identification of a novel crizotinib-sensitive MET-ATXN7L1 gene fusion variant in lung adenocarcinoma by next generation sequencing., Ann Oncol
Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.
Taipale et al., 2013, Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells., Nat. Biotechnol.
Vaishnavi et al., 2013, Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer., Nat. Med.
Yoshida et al., 2016, Differential Crizotinib Response Duration Among ALK Fusion Variants in ALK-Positive Non-Small-Cell Lung Cancer., J. Clin. Oncol.
Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature
Nair A et al., 2018, Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly effective therapeutic strategy in triple-negative breast cancer., Nat Med
Katayama R et al., 2015, P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer., EBioMedicine

CRIZOTINIB EML4

Interaction Score: 4.83

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
26775591 22235099 23344087 24675041 27354483 20979469 26554404 25228534 22277784 21613408 28476735 21791641 27780853 27009859 27432227 26698910

Sources:
JAX-CKB
CRIZOTINIB ALK

Interaction Score: 4.0

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:C1156Y,L1196M

Alteration ALK:L1198F

Alteration ALK:F856S,A348D

PMIDs:
25228534 22277784 24687827 20979472 2270034 24491302 25945060 25588040 24433361 21791641 21948233 21030459 18724359 21575866 20979473 24327273 24670165 23344087 22235099 18923523 21242967 23598171 21838707 26619011 18923525 22072639 26554404 24468632 21345110 27022118 24478318 25470694 23724913 24675041 26444240 26698910 20979469 21258415 26221234 18089725 25408655 28586279 25922291 26466010 21933749 22594847 28787259 24573551 21613408 27009859 26775591 25724526 25421750 25806224 26438783 27780853 24509625 25749034 27432227 29650534 30679328 23006951 23239810 30368418 26498130

Sources:
TALC DTC DrugBank MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions CGI DoCM COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB
CRIZOTINIB ROS1

Interaction Score: 2.37

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status case report

Pathway activation

Variant Effect gain-of-function

PMIDs:
25351743 23724914 26372962 25688157 25733882 25667280 25264305 24875859 29596029 25922291 22215748 29333528 30980071

Sources:
TALC MyCancerGenome JAX-CKB CGI DoCM CIViC CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB
CRIZOTINIB PTPN12

Interaction Score: 1.89

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
29578538

Sources:
CIViC
CRIZOTINIB MET

Interaction Score: 1.42

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
12460923 11750879 9826708 25157968 10417759 1104268 17483355 22594847 31391294 25971938 26729443 25971939 26547802 23729478 25232318 25922291 27325282 21716144 22162573 21623265 22162641 28396313 28514312 15494073 26779812 21266357 26432108 26483207 27393507 27149990 27283993 27595477 27694386 27343442 28765324 28522754 31584608 31416808 26892698 31932802 31809977 30339198 10592235

Sources:
TALC ClearityFoundationBiomarkers DrugBank MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions CGI DoCM COSMIC CIViC GuideToPharmacology MyCancerGenomeClinicalTrial PharmGKB TTD OncoKB
CRIZOTINIB AREG

Interaction Score: 1.14

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
21791641

Sources:
CIViC
CRIZOTINIB NPM1

Interaction Score: 1.07

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type anaplastic large cell lymphoma

Response Type resistant

Approval Status Preclinical

PMIDs:
18089725 27009859 24509625 25749034 25421750

Sources:
JAX-CKB
CRIZOTINIB SMAD4

Interaction Score: 0.47

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type resistant

Approval Status Clinical Study

PMIDs:
28476735

Sources:
JAX-CKB
CRIZOTINIB ETV6

Interaction Score: 0.47

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type sensitive

PMIDs:
23811600

Sources:
JAX-CKB
CRIZOTINIB CDKN2A

Interaction Score: 0.26

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type resistant

Approval Status Clinical Study

PMIDs:
28476735

Sources:
JAX-CKB
CRIZOTINIB NTRK1

Interaction Score: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ALK inhibitor

Alteration NTRK1__.

PMIDs:
24162815

Sources:
CGI CIViC
CRIZOTINIB EGFR

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy CO1686 + Crizotinib

Indication/Tumor Type non-small cell lung carcinoma

Indication/Tumor Type lung adenocarcinoma

PMIDs:
27393507 27283993 27595477 21791641

Sources:
JAX-CKB CIViC
CRIZOTINIB KRAS

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type stomach cancer

Response Type resistant

Approval Status Preclinical

PMIDs:
25232318 27338794 26432108

Sources:
JAX-CKB
CRIZOTINIB ERBB2

Interaction Score: 0.07

Interaction Types & Directionality:

n/a

Interaction Info:

Alteration MET:amp;ERBB2:amp

Drug family ALK inhibitor;ERBB2 mAb inhibitor

combination therapy Crizotinib;Trastuzumab

PMIDs:
27595477 26432108

Sources:
JAX-CKB CGI
CRIZOTINIB FGFR1

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type resistant

Approval Status Clinical Study

PMIDs:
28476735

Sources:
JAX-CKB
CRIZOTINIB ABL1

Interaction Score: 0.04

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ALK inhibitor

Alteration ABL1:V299L

PMIDs:
None found

Sources:
CGI
CRIZOTINIB TP53

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Crizotinib + Cyclophosphamide + Topotecan

Indication/Tumor Type neuroblastoma

Response Type no benefit

PMIDs:
27149990 25971938 26438783

Sources:
JAX-CKB
CRIZOTINIB SRC

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung cancer

Response Type resistant

Approval Status Preclinical

PMIDs:
None found

Sources:
JAX-CKB
CRIZOTINIB BRAF

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Crizotinib;Vemurafenib

Drug family ALK inhibitor;BRAF inhibitor

Alteration MET:amp;BRAF:V600E

PMIDs:
None found

Sources:
CGI
CRIZOTINIB ABCB1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26870817

Sources:
CIViC

DrugBank: DB08865
- Version: 5.1.7
Alternate Names:

CRIZOTINIB DrugBank Drug Name

877399-52-5 CAS Number

Xalkori Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Categories amines

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Forde et al., 2012, Crizotinib in the treatment of non-small-cell lung cancer., Expert Opin Pharmacother
CancerCommons: CRIZOTINIB
- Version: 25-July-2013
Alternate Names:

Crizotinib PubChem Drug Name

11626560 PubChem Drug ID

Xalkori Drug Trade Name

Drug Info:

Drug Class ALK Inhibitor

Source Reported Drug Name(s) Crizotinib/Xalkori/PF-02341066

Pharmaceutical Developer Pfizer

Publications:
MyCancerGenome: CRIZOTINIB
- Version: 20-Jun-2017
Alternate Names:

PF-02341066 Development Name

CRIZOTINIB Generic Name

XALKORI Trade Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Non-small cell lung cancer (with ALK fusion or ROS1 gene alteration)

Publications:
TdgClinicalTrial: CRIZOTINIB
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval approved

Publications:

DTC: CRIZOTINIB

Version: 02-September-2020

Alternate Names:

CHEMBL601719 ChEMBL Drug ID

Drug Info:

Publications:

Tardy S et al., 2014, Synthesis and biological evaluation of benzo[4,5]imidazo[1,2-c]pyrimidine and benzo[4,5]imidazo[1,2-a]pyrazine derivatives as anaplastic lymphoma kinase inhibitors., Bioorg Med Chem

JAX-CKB: Crizotinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Ceccon et al., 2015, Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma., Mol. Cancer Res.

Mologni et al., 2015, NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922., Oncotarget

Zdzalik et al., 2014, Activating mutations in ALK kinase domain confer resistance to structurally unrelated ALK inhibitors in NPM-ALK-positive anaplastic large-cell lymphoma., J. Cancer Res. Clin. Oncol.

CGI: Crizotinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Gambacorti Passerini et al., 2014, Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients., J. Natl. Cancer Inst.

Orimo et al., 1990, [The role of hyperlipidemia in the development of atherosclerosis]., Nippon Rinsho

Butrynski et al., 2010, Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor., N. Engl. J. Med.

DoCM: CRIZOTINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Infarinato et al., 2016, The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma., Cancer Discov

Bresler et al., 2011, Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma., Sci Transl Med

George et al., 2008, Activating mutations in ALK provide a therapeutic target in neuroblastoma., Nature

PharmGKB: crizotinib

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Ou SH, 2011, Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond., Drug Des Devel Ther

Ehmann F et al., 2014, European Medicines Agency initiatives and perspectives on pharmacogenomics., Br J Clin Pharmacol

Pall G, 2015, The next-generation ALK inhibitors., Curr Opin Oncol

CIViC: CRIZOTINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Choi et al., 2010, EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors., N. Engl. J. Med.

Normant et al., 2011, The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models., Oncogene

Kwak et al., 2010, Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer., N. Engl. J. Med.

TALC: CRIZOTINIB
- Version: 12-May-2016
Alternate Names:

CRIZOTINIB Primary Drug Name

CRIZOTINIB Drug Generic Name

XALKORI Drug Trade Name

Drug Info:

Publications:
TTD: Crizotinib
- Version: 2020.06.01
Alternate Names:

D03ZBT TTD Drug ID

Drug Info:

Publications:
GuideToPharmacology: 178101602
- Version: 29-September-2020
Alternate Names:

CRIZOTINIB GuideToPharmacology Ligand Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL601719
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
ClearityFoundationBiomarkers: CRIZOTINIB
- Version: 26-July-2013
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: CRIZOTINIB
- Version: 30-February-2014
Alternate Names:

Drug Info:

Publications:
FDA: Crizotinib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:
OncoKB: Crizotinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL601719
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
COSMIC: Crizotinib
- Version: 4-Sep-2020
Alternate Names:

Drug Info:

Publications:

Indication/Tumor Type	Advanced Solid Tumor
Response Type	sensitive
Approval Status	Preclinical

Alteration	ALK:C1156Y,L1196M
Alteration	ALK:L1198F
Alteration	ALK:F856S,A348D

Clinical Status	case report
Pathway	activation
Variant Effect	gain-of-function

Specific Action of the Ligand	Inhibition
Endogenous Drug?	False
Direct Interaction?	False

Indication/Tumor Type	anaplastic large cell lymphoma
Response Type	resistant
Approval Status	Preclinical

Indication/Tumor Type	pancreatic ductal adenocarcinoma
Response Type	resistant
Approval Status	Clinical Study

Evidence Type	Actionable
Approval Status	Preclinical - Cell line xenograft
Response Type	sensitive

combination therapy	CO1686 + Crizotinib
Indication/Tumor Type	non-small cell lung carcinoma
Indication/Tumor Type	lung adenocarcinoma

Indication/Tumor Type	stomach cancer
Response Type	resistant
Approval Status	Preclinical

Alteration	MET:amp;ERBB2:amp
Drug family	ALK inhibitor;ERBB2 mAb inhibitor
combination therapy	Crizotinib;Trastuzumab

combination therapy	Crizotinib + Cyclophosphamide + Topotecan
Indication/Tumor Type	neuroblastoma
Response Type	no benefit

Indication/Tumor Type	lung cancer
Response Type	resistant
Approval Status	Preclinical

combination therapy	Crizotinib;Vemurafenib
Drug family	ALK inhibitor;BRAF inhibitor
Alteration	MET:amp;BRAF:V600E

CRIZOTINIB	DrugBank Drug Name
877399-52-5	CAS Number
Xalkori	Drug Brand

Drug Type	small molecule
Drug Groups	approved
Drug Categories	amines

Crizotinib	PubChem Drug Name
11626560	PubChem Drug ID
Xalkori	Drug Trade Name

PF-02341066	Development Name
CRIZOTINIB	Generic Name
XALKORI	Trade Name

CRIZOTINIB	Primary Drug Name
CRIZOTINIB	Drug Generic Name
XALKORI	Drug Trade Name

CRIZOTINIB Drug Record

CRIZOTINIB chembl:CHEMBL601719 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type Advanced Solid Tumor Response Type sensitive Approval Status Preclinical

PMIDs: 26775591 22235099 23344087 24675041 27354483 20979469 26554404 25228534 22277784 21613408 28476735 21791641 27780853 27009859 27432227 26698910

Sources: JAX-CKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Alteration ALK:C1156Y,L1196M Alteration ALK:L1198F Alteration ALK:F856S,A348D

Sources: TALC DTC DrugBank MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions CGI DoCM COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Clinical Status case report Pathway activation Variant Effect gain-of-function

PMIDs: 25351743 23724914 26372962 25688157 25733882 25667280 25264305 24875859 29596029 25922291 22215748 29333528 30980071

Sources: TALC MyCancerGenome JAX-CKB CGI DoCM CIViC CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 29578538

Sources: CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Specific Action of the Ligand Inhibition Endogenous Drug? False Direct Interaction? False

Sources: TALC ClearityFoundationBiomarkers DrugBank MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions CGI DoCM COSMIC CIViC GuideToPharmacology MyCancerGenomeClinicalTrial PharmGKB TTD OncoKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 21791641

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type anaplastic large cell lymphoma Response Type resistant Approval Status Preclinical

PMIDs: 18089725 27009859 24509625 25749034 25421750

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type pancreatic ductal adenocarcinoma Response Type resistant Approval Status Clinical Study

PMIDs: 28476735

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical - Cell line xenograft Response Type sensitive

PMIDs: 23811600

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type pancreatic ductal adenocarcinoma Response Type resistant Approval Status Clinical Study

PMIDs: 28476735

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Drug family ALK inhibitor Alteration NTRK1__.

PMIDs: 24162815

Sources: CGI CIViC

Interaction Types & Directionality: n/a

Interaction Info: combination therapy CO1686 + Crizotinib Indication/Tumor Type non-small cell lung carcinoma Indication/Tumor Type lung adenocarcinoma

PMIDs: 27393507 27283993 27595477 21791641

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type stomach cancer Response Type resistant Approval Status Preclinical

PMIDs: 25232318 27338794 26432108

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Alteration MET:amp;ERBB2:amp Drug family ALK inhibitor;ERBB2 mAb inhibitor combination therapy Crizotinib;Trastuzumab

PMIDs: 27595477 26432108

Sources: JAX-CKB CGI

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type pancreatic ductal adenocarcinoma Response Type resistant Approval Status Clinical Study

PMIDs: 28476735

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Drug family ALK inhibitor Alteration ABL1:V299L

PMIDs: None found

Sources: CGI

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Crizotinib + Cyclophosphamide + Topotecan Indication/Tumor Type neuroblastoma Response Type no benefit

PMIDs: 27149990 25971938 26438783

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung cancer Response Type resistant Approval Status Preclinical

PMIDs: None found

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Crizotinib;Vemurafenib Drug family ALK inhibitor;BRAF inhibitor Alteration MET:amp;BRAF:V600E

PMIDs: None found

Sources: CGI

Interaction Types & Directionality: n/a

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type Advanced Solid Tumor

Response Type sensitive

Approval Status Preclinical

PMIDs:
26775591 22235099 23344087 24675041 27354483 20979469 26554404 25228534 22277784 21613408 28476735 21791641 27780853 27009859 27432227 26698910

Sources:
JAX-CKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:C1156Y,L1196M

Alteration ALK:L1198F

Alteration ALK:F856S,A348D

Sources:
TALC DTC DrugBank MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions CGI DoCM COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status case report

Pathway activation

Variant Effect gain-of-function

PMIDs:
25351743 23724914 26372962 25688157 25733882 25667280 25264305 24875859 29596029 25922291 22215748 29333528 30980071

Sources:
TALC MyCancerGenome JAX-CKB CGI DoCM CIViC CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality:

n/a

PMIDs:
29578538

Sources:
CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

Sources:
TALC ClearityFoundationBiomarkers DrugBank MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions CGI DoCM COSMIC CIViC GuideToPharmacology MyCancerGenomeClinicalTrial PharmGKB TTD OncoKB

Interaction Types & Directionality:

n/a

PMIDs:
21791641

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type anaplastic large cell lymphoma

Response Type resistant

Approval Status Preclinical

PMIDs:
18089725 27009859 24509625 25749034 25421750

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type resistant

Approval Status Clinical Study

PMIDs:
28476735

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell line xenograft

Response Type sensitive

PMIDs:
23811600

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type resistant

Approval Status Clinical Study

PMIDs:
28476735

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ALK inhibitor

Alteration NTRK1__.

PMIDs:
24162815

Sources:
CGI CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy CO1686 + Crizotinib

Indication/Tumor Type non-small cell lung carcinoma

Indication/Tumor Type lung adenocarcinoma

PMIDs:
27393507 27283993 27595477 21791641

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type stomach cancer

Response Type resistant

Approval Status Preclinical

PMIDs:
25232318 27338794 26432108

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Alteration MET:amp;ERBB2:amp

Drug family ALK inhibitor;ERBB2 mAb inhibitor

combination therapy Crizotinib;Trastuzumab

PMIDs:
27595477 26432108

Sources:
JAX-CKB CGI

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type resistant

Approval Status Clinical Study

PMIDs:
28476735

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family ALK inhibitor

Alteration ABL1:V299L

PMIDs:
None found

Sources:
CGI

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Crizotinib + Cyclophosphamide + Topotecan

Indication/Tumor Type neuroblastoma

Response Type no benefit

PMIDs:
27149990 25971938 26438783

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung cancer

Response Type resistant

Approval Status Preclinical

PMIDs:
None found

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Crizotinib;Vemurafenib

Drug family ALK inhibitor;BRAF inhibitor

Alteration MET:amp;BRAF:V600E

PMIDs:
None found

Sources:
CGI

Interaction Types & Directionality:

n/a

PMIDs:
26870817

Sources:
CIViC

Alternate Names:

CRIZOTINIB DrugBank Drug Name

877399-52-5 CAS Number

Xalkori Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Categories amines

Publications:

Berman et al., 2000, The Protein Data Bank., Nucleic Acids Res.

Forde et al., 2012, Crizotinib in the treatment of non-small-cell lung cancer., Expert Opin Pharmacother

Alternate Names:

Crizotinib PubChem Drug Name

11626560 PubChem Drug ID

Xalkori Drug Trade Name

Drug Info:

Drug Class ALK Inhibitor

Source Reported Drug Name(s) Crizotinib/Xalkori/PF-02341066

Pharmaceutical Developer Pfizer