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ALK Gene Record

  • Summary
  • Interactions
  • Claims
  • ALK 238 Druggable GenomeClinically ActionableDrug Resistance

    Alternate Names:

    238
    ALK RECEPTOR TYROSINE KINASE
    ALK
    CD246
    NBLST3
    105590
    427
    ENSG00000171094
    OTTHUMG00000152034
    ALK tyrosine kinase receptor
    CD_antigen=CD246
    Anaplastic lymphoma kinase
    Q9UM73
    ALK_HUMAN
    ALK TYROSINE KINASE RECEPTOR PRECURSOR (EC 2.7.1.112) (ANAPLASTIC LYMPHOMA KINASE) (CD246 ANTIGEN). [SOURCE:UNIPROT/SWISSPROT;ACC:Q9UM73]
    1
    PA24719
    T56418
    ALK1

    Gene Info:

    Interpro Acc IPR001245
    Interpro Name Serine-threonine/tyrosine-protein kinase catalytic domain
    Uniprot Status Swiss-Prot
    Human Readable Name DRUGGABLE GENOME
    Interpro Short Name Ser-Thr/Tyr_kinase_cat_dom
    Uniprot Evidence 1: Evidence at protein level
    Human Readable Name KINASE
    Interpro Type Domain
    CancerCommons Reported Gene Name ALK, ROS
    CancerCommons Reported Gene Name ALK
    Target Class Receptors
    Target Subclass EC:2.7.10.1
    Gene Biotype PROTEIN_CODING
    (24 More Sources)

    Gene Categories: Category Details

    KINASE
    TYROSINE KINASE
    DRUG RESISTANCE
    DRUGGABLE GENOME
    CLINICALLY ACTIONABLE

    Publications:

    Amin et al., 2016, TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors., 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.
    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
    Katayama et al., 2014, Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib., Clin. Cancer Res.
    Lovly et al., 2011, Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors., Cancer Res.
    Johung et al., 2016, Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis., J. Clin. Oncol.
    Yang Y et al., 2020, Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial., Lancet Respir Med
    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
    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.
    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.
    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.
    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.
    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
    Ou et al., 2014, Identification of a novel HIP1-ALK fusion variant in Non-Small-Cell Lung Cancer (NSCLC) and discovery of ALK I1171 (I1171N/S) mutations in two ALK-rearranged NSCLC patients with resistance to Alectinib., J Thorac Oncol
    Lu et al., 2017, The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model., Cancer Lett.
    Yoshimura et al., 2016, Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation: Efficacy of alectinib against ALK G1269A mutated cells., Cancer Chemother. Pharmacol.
    Ou et al., 2017, Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy?, Lung Cancer
    Ou et al., 2016, Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study., J. Clin. Oncol.
    Johnson et al., 2016, Identification of I1171N resistance mutation in ALK-positive non-small-cell lung cancer tumor sample and circulating tumor DNA., Lung Cancer
    Yoshida et al., 2016, Rapid and dramatic response to alectinib in an anaplastic lymphoma kinase rearranged non-small-cell lung cancer patient who is critically ill., Anticancer Drugs
    Shaw et al., 2016, Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial., Lancet Oncol.
    Seto et al., 2013, CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study., Lancet Oncol.
    Gadgeel et al., 2014, Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study., Lancet Oncol.
    Fontana et al., 2015, Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK., Cancer Med
    Hida T et al., 2017, Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial., Lancet
    Paik J et al., 2018, Alectinib: A Review in Advanced, ALK-Positive NSCLC., Drugs
    Crystal et al., 2014, Patient-derived models of acquired resistance can identify effective drug combinations for cancer., Science
    Hawinkels et al., 2016, Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors., Clin. Cancer Res.
    Makker et al., 2015, Phase II evaluation of dalantercept, a soluble recombinant activin receptor-like kinase 1 (ALK1) receptor fusion protein, for the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study 0229N., Gynecol. Oncol.
    Zou et al., 2015, PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models., Cancer Cell
    Solomon BJ et al., 2018, Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study., Lancet Oncol
    Amatu et al., 2015, Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer., Br. J. Cancer
    Ardini et al., 2016, Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications., Mol. Cancer Ther.
    Drilon et al., 2017, Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1)., Cancer Discov
    Landi L et al., 2016, Ceritinib for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer., Expert Rev Clin Pharmacol
    Marsilje et al., 2013, Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials., J. Med. Chem.
    Galkin et al., 2007, Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK., Proc. Natl. Acad. Sci. U.S.A.
    Soria et al., 2017, First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study., Lancet
    Crinò et al., 2016, Multicenter Phase II Study of Whole-Body and Intracranial Activity With Ceritinib in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib: Results From ASCEND-2., J. Clin. Oncol.
    Mansfield et al., 2016, Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib., Ann. Oncol.
    Yakirevich et al., 2016, Oncogenic ALK Fusion in Rare and Aggressive Subtype of Colorectal Adenocarcinoma as a Potential Therapeutic Target., Clin. Cancer Res.
    Ou et al., 2015, I1171 missense mutation (particularly I1171N) is a common resistance mutation in ALK-positive NSCLC patients who have progressive disease while on alectinib and is sensitive to ceritinib., Lung Cancer
    Kim et al., 2016, Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial., Lancet Oncol.
    Shaw AT et al., 2017, Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial., Lancet Oncol
    Gainor et al., 2016, EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis., Clin. Cancer Res.
    Siaw et al., 2016, Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice., Oncotarget
    Kim et al., 2017, Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial., J. Clin. Oncol.
    Gettinger et al., 2016, Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial., Lancet Oncol.
    Wu et al., 2016, Second- and third-generation ALK inhibitors for non-small cell lung cancer., J Hematol Oncol
    Markham A, 2017, Brigatinib: First Global Approval., Drugs
    Iragavarapu C et al., 2015, Novel ALK inhibitors in clinical use and development., J Hematol Oncol
    Solomon et al., 2014, Current status of targeted therapy for anaplastic lymphoma kinase-rearranged non-small cell lung cancer., Clin. Pharmacol. Ther.
    Katayama et al., 2011, Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK., Proc. Natl. Acad. Sci. U.S.A.
    Gunby et al., 2006, Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and homology modeling., J. Med. Chem.
    Mourali et al., 2006, Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage., Mol. Cell. Biol.
    Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.
    Lee et al., 2011, Anaplastic lymphoma kinase translocation: a predictive biomarker of pemetrexed in patients with non-small cell lung cancer., J Thorac Oncol
    Rust et al., 2005, TIMP-1 expression in anaplastic large cell lymphoma is usually restricted to macrophages and only seldom observed in tumour cells., J. Pathol.
    Soda et al., 2007, Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer., Nature
  • BRIGATINIB   ALK

    Interaction Score: 6.49

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Direct Interaction yes
    Mechanism of Interaction ALK tyrosine kinase receptor inhibitor

    PMIDs:
    25588040 27049722 28475456 25727400 29650534 27836716 26951079 28597393 25888090 23239810


    Sources:
    ChemblInteractions COSMIC CIViC PharmGKB TTD FDA OncoKB

  • ALECTINIB   ALK

    Interaction Score: 5.89

    Interaction Types & Directionality:
    inhibitor (inhibitory)

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

    PMIDs:
    25588040 25393796 25806224 21575866 28455243 23344087 26849637 27009859 28586279 28285684 26598747 26438117 26698910 25421750 25749034 27565911 27432227 25228534 22277784 26938871 26708155 23639470 25153538 25727400 29650534 28501140 30030733


    Sources:
    TALC MyCancerGenome JAX-CKB COSMIC CIViC PharmGKB TTD FDA OncoKB

  • ENSARTINIB   ALK

    Interaction Score: 5.72

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Notes
    Indication/Tumor Type non-small cell lung carcinoma
    Response Type sensitive

    PMIDs:
    21613408 26438117 31628085


    Sources:
    TALC MyCancerGenome JAX-CKB ChemblInteractions CIViC CancerCommons TTD

  • CRIZOTINIB   ALK

    Interaction Score: 5.09

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Reported Cancer Type Lung
    Clinical Status case report
    Variant Effect gain-of-function

    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 MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions DoCM COSMIC CIViC CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

  • CERITINIB   ALK

    Interaction Score: 4.79

    Interaction Types & Directionality:
    antagonist (inhibitory)
    inhibitor (inhibitory)

    Interaction Info:
    Notes Specifically targets ALK translocations
    Reported Cancer Type Lung
    combination therapy Saracatinib + Ceritinib

    PMIDs:
    26582431 25945060 23742252 17185414 24670165 25806224 27009859 26775591 25394791 26438117 28126333 27432917 25724526 24675041 26698910 27432227 25421750 27780853 25749034 25228534 21575866 20979473 24327273 23344087 22235099 22277784 27742657 26933125 26633560 25736571 26973324 29650534 28602779


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

  • CHEMBL3397300   ALK

    Interaction Score: 3.24

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Notes
    Indication/Tumor Type Advanced Solid Tumor
    Response Type decreased response

    PMIDs:
    24091716 21502504 27009859 27836716 26438117 27432227 26698910 25421750 27049722 27780853 25749034 25228534


    Sources:
    TALC MyCancerGenome JAX-CKB MyCancerGenomeClinicalTrial TTD

  • LORLATINIB   ALK

    Interaction Score: 2.86

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Approval Status Preclinical - Cell line xenograft
    Response Type conflicting
    Indication/Tumor Type lung cancer

    PMIDs:
    28285684 26698910 26554404 25749034 26144315 27432227 30413378 29650534


    Sources:
    JAX-CKB COSMIC CIViC PharmGKB TTD FDA OncoKB

  • ASP-3026   ALK

    Interaction Score: 2.58

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Reported Cancer Type Lung
    Indication/Tumor Type Advanced Solid Tumor
    Response Type resistant

    PMIDs:
    27009859 25421750 25749034 25228534


    Sources:
    MyCancerGenome JAX-CKB ChemblInteractions CancerCommons TTD

  • CHEMBL473773   ALK

    Interaction Score: 1.14

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    17625570


    Sources:
    CIViC

  • LUMINESPIB   ALK

    Interaction Score: 1.14

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    26698910


    Sources:
    CIViC

  • DALANTERCEPT   ALK

    Interaction Score: 0.86

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    combination therapy Dalantercept + Cisplatin
    Indication/Tumor Type breast cancer
    Response Type predicted – sensitive

    PMIDs:
    26373572 25888978


    Sources:
    JAX-CKB

  • INTERLEUKIN-10   ALK

    Interaction Score: 0.57

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    15920698


    Sources:
    NCI

  • ONALESPIB   ALK

    Interaction Score: 0.57

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    combination therapy Crizotinib + Onalespib
    Indication/Tumor Type non-small cell lung carcinoma
    Response Type no benefit

    PMIDs:
    None found


    Sources:
    JAX-CKB

  • ALECTINIB HYDROCHLORIDE   ALK

    Interaction Score: 0.57

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction ALK tyrosine kinase receptor inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • CEP-37440   ALK

    Interaction Score: 0.57

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction ALK tyrosine kinase receptor inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • DURVALUMAB   ALK

    Interaction Score: 0.38

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    Indication/Tumor Type non-small cell lung carcinoma
    Response Type decreased response
    Approval Status Clinical Study

    PMIDs:
    27225694


    Sources:
    JAX-CKB

  • ATEZOLIZUMAB   ALK

    Interaction Score: 0.35

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    Evidence Type Actionable
    Approval Status Clinical Study
    Response Type decreased response

    PMIDs:
    27225694


    Sources:
    JAX-CKB PharmGKB FDA

  • NIVOLUMAB   ALK

    Interaction Score: 0.31

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    Evidence Type Actionable
    Approval Status Clinical Study
    Response Type decreased response

    PMIDs:
    27225694


    Sources:
    JAX-CKB PharmGKB FDA

  • PEMBROLIZUMAB   ALK

    Interaction Score: 0.21

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    Indication/Tumor Type non-small cell lung carcinoma
    Response Type decreased response
    Approval Status Clinical Study

    PMIDs:
    27225694


    Sources:
    JAX-CKB PharmGKB FDA

  • SARACATINIB   ALK

    Interaction Score: 0.19

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    combination therapy Saracatinib + Ceritinib
    Indication/Tumor Type non-small cell lung carcinoma
    Response Type sensitive

    PMIDs:
    25394791


    Sources:
    JAX-CKB

  • CRENOLANIB   ALK

    Interaction Score: 0.19

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:

    PMIDs:
    None found


    Sources:
    MyCancerGenomeClinicalTrial

  • RAMUCIRUMAB   ALK

    Interaction Score: 0.19

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    PharmGKB

  • PEMETREXED   ALK

    Interaction Score: 0.16

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    21642865


    Sources:
    CIViC

  • TOPOTECAN   ALK

    Interaction Score: 0.15

    Interaction Types & Directionality:
    n/a

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

    PMIDs:
    26438783


    Sources:
    JAX-CKB

  • GANETESPIB   ALK

    Interaction Score: 0.13

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:

    PMIDs:
    None found


    Sources:
    MyCancerGenomeClinicalTrial

  • ENTRECTINIB   ALK

    Interaction Score: 0.12

    Interaction Types & Directionality:
    n/a

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

    PMIDs:
    26633560 26939704 28183697


    Sources:
    DTC JAX-CKB CIViC

  • SELUMETINIB   ALK

    Interaction Score: 0.07

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    combination therapy Ceritinib + Selumetinib
    Indication/Tumor Type non-small cell lung carcinoma
    Response Type sensitive

    PMIDs:
    25394791


    Sources:
    JAX-CKB

  • DOXORUBICIN   ALK

    Interaction Score: 0.06

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    combination therapy Dalantercept + Doxorubicin
    Indication/Tumor Type melanoma
    Response Type sensitive

    PMIDs:
    16880530 28455243 26373572


    Sources:
    JAX-CKB NCI

  • TAK-715   ALK

    Interaction Score: 0.05

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • IMATINIB   ALK

    Interaction Score: 0.04

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    16970400


    Sources:
    NCI

  • CHEMBL546797   ALK

    Interaction Score: 0.04

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • CYCLOPHOSPHAMIDE   ALK

    Interaction Score: 0.03

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    Approval Status Preclinical - Cell line xenograft
    combination therapy Crizotinib + Cyclophosphamide + Topotecan
    Indication/Tumor Type neuroblastoma

    PMIDs:
    26438783


    Sources:
    JAX-CKB

  • HESPERADIN   ALK

    Interaction Score: 0.03

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:

    PMIDs:
    19035792


    Sources:
    DTC

  • PAZOPANIB   ALK

    Interaction Score: 0.03

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • CHEMBL1997335   ALK

    Interaction Score: 0.03

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • OSI-632   ALK

    Interaction Score: 0.03

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • CHEMBL379975   ALK

    Interaction Score: 0.03

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • DACTOLISIB   ALK

    Interaction Score: 0.03

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • CEDIRANIB   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • PALBOCICLIB   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • ERLOTINIB   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • JNJ-7706621   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • PD-0166285   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • VANDETANIB   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • GW441756X   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • LINIFANIB   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • TOZASERTIB   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • CISPLATIN   ALK

    Interaction Score: 0.02

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    combination therapy Dalantercept + Cisplatin
    Indication/Tumor Type breast cancer
    Response Type predicted – sensitive

    PMIDs:
    26373572


    Sources:
    JAX-CKB

  • R-406   ALK

    Interaction Score: 0.01

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • RG-1530   ALK

    Interaction Score: 0.01

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • DOVITINIB   ALK

    Interaction Score: 0.01

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • ILORASERTIB   ALK

    Interaction Score: 0.01

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • PF-00562271   ALK

    Interaction Score: 0.01

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • CENISERTIB   ALK

    Interaction Score: 0.01

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • Ensembl: ENSG00000171094

    • Version: 101_38

    Alternate Names:
    ALK Ensembl Gene Name

    Gene Info:
    Gene Biotype PROTEIN_CODING

    Publications:

  • TdgClinicalTrial: Q9UM73

    • Version: January-2014

    Alternate Names:
    ALK Gene Symbol

    Gene Info:
    Target Class Receptors
    Target Subclass EC:2.7.10.1

    Publications:

  • HopkinsGroom: Q9UM73

    • Version: 11-September-2012

    Alternate Names:
    238 Entrez Gene Id
    ALK_HUMAN Uniprot Id
    Q9UM73 Uniprot Accession

    Gene Info:
    Interpro Acc IPR001245
    Interpro Name Serine-threonine/tyrosine-protein kinase catalytic domain
    Uniprot Status Swiss-Prot

    Gene Categories:
    KINASE, DRUGGABLE GENOME

    Publications:

  • CancerCommons: ALK

    • Version: 25-July-2013

    Alternate Names:
    238 Entrez Gene ID

    Gene Info:
    CancerCommons Reported Gene Name ALK, ROS
    CancerCommons Reported Gene Name ALK

    Publications:

  • RussLampel: ENSG00000171094

    • Version: 26-July-2011

    Alternate Names:
    ALK Display Id
    ALK TYROSINE KINASE RECEPTOR PRECURSOR (EC 2.7.1.112) (ANAPLASTIC LYMPHOMA KINASE) (CD246 ANTIGEN). [SOURCE:UNIPROT/SWISSPROT;ACC:Q9UM73] Description
    ENSG00000171094 Ensembl Gene Id

    Gene Info:
    Human Readable Name DRUGGABLE GENOME

    Gene Categories:
    DRUGGABLE GENOME

    Publications:

  • JAX-CKB: ALK

    • Version: 27-September-2017

    Alternate Names:
    238 CKB Entrez Id
    ALK CKB Gene Synonym
    CD246 CKB Gene Synonym

    Gene Info:

    Publications:
    Hawinkels et al., 2016, Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors., Clin. Cancer Res.
    Amin et al., 2016, TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors., Oncotarget
    Wang et al., 2016, Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis., Sci Rep

  • PharmGKB: ALK

    • Version: 18-August-2020

    Alternate Names:
    PA24719 PharmGKB ID

    Gene Info:

    Publications:
    Pall G, 2015, The next-generation ALK inhibitors., Curr Opin Oncol
    Landi L et al., 2016, Ceritinib for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer., Expert Rev Clin Pharmacol
    Kanaan Z et al., 2015, Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond., Onco Targets Ther

  • CIViC: ALK

    • Version: 14-September-2020

    Alternate Names:
    238 Entrez Gene ID
    1 CIViC Gene ID

    Gene Info:

    Gene Categories:
    DRUG RESISTANCE, CLINICALLY ACTIONABLE

    Publications:
    Normant et al., 2011, The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models., Oncogene
    Katayama et al., 2012, Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers., Sci Transl Med
    Cerchietti et al., 2011, Inhibition of anaplastic lymphoma kinase (ALK) activity provides a therapeutic approach for CLTC-ALK-positive human diffuse large B cell lymphomas., PLoS ONE

  • NCI: ALK

    • Version: 14-September-2017

    Alternate Names:

    Gene Info:

    Publications:
    Rust et al., 2005, TIMP-1 expression in anaplastic large cell lymphoma is usually restricted to macrophages and only seldom observed in tumour cells., J. Pathol.
    Gunby et al., 2006, Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and homology modeling., J. Med. Chem.
    Mourali et al., 2006, Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage., Mol. Cell. Biol.

  • DoCM: ALK

    • Version: 27-September-2017

    Alternate Names:

    Gene Info:

    Publications:
    Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
    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.
    Bresler et al., 2011, Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma., Sci Transl Med

  • DTC: ALK

    • Version: 02-September-2020

    Alternate Names:

    Gene Info:

    Publications:
    Bamborough et al., 2008, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery., J. Med. Chem.
    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

  • TALC: ALK

    • Version: 12-May-2016

    Alternate Names:
    ALK Gene Symbol

    Gene Info:

    Publications:

  • HingoraniCasas: ENSG00000171094

    • Version: 31-May-2017

    Alternate Names:
    ENSG00000171094 Gene Symbol
    ALK Ensembl Id

    Gene Info:

    Gene Categories:
    DRUGGABLE GENOME

    Publications:

  • MyCancerGenome: ALK

    • Version: 20-Jun-2017

    Alternate Names:
    238 Entrez Gene Id
    ALK MyCancerGenome Gene Symbol
    ALK MyCancerGenome Reported Gene Name

    Gene Info:

    Publications:

  • ChemblInteractions: ALK

    • Version: chembl_23

    Alternate Names:
    ALK GENE_SYMBOL
    ALK tyrosine kinase receptor UNIPROT
    Anaplastic lymphoma kinase UNIPROT

    Gene Info:

    Publications:

  • OncoKB: ALK

    • Version: 23-July-2020

    Alternate Names:
    238 OncoKB Entrez Id
    NBLST3 OncoKB Gene Synonym
    CD246 OncoKB Gene Synonym

    Gene Info:

    Publications:

  • Tempus: ALK

    • Version: 11-November-2018

    Alternate Names:
    ALK Gene Symbol

    Gene Info:

    Gene Categories:
    CLINICALLY ACTIONABLE

    Publications:

  • dGene: ALK

    • Version: 27-Jun-2013

    Alternate Names:
    238 Gene ID
    CD246 dGene Synonym
    NBLST3 dGene Synonym

    Gene Info:

    Gene Categories:
    KINASE, TYROSINE KINASE

    Publications:

  • TTD: ALK tyrosine kinase receptor

    • Version: 2020.06.01

    Alternate Names:
    ALK TTD Gene Abbreviation
    T56418 TTD Target ID

    Gene Info:

    Publications:

  • Pharos: ALK

    • Version: 01-February-2022

    Alternate Names:
    ALK tyrosine kinase receptor Gene Name
    Q9UM73 UniProt ID

    Gene Info:

    Gene Categories:
    KINASE

    Publications:

  • MyCancerGenomeClinicalTrial: ALK

    • Version: 30-February-2014

    Alternate Names:

    Gene Info:

    Publications:

  • MskImpact: ALK

    • Version: May-2015

    Alternate Names:

    Gene Info:

    Gene Categories:
    CLINICALLY ACTIONABLE

    Publications:

  • FoundationOneGenes: ALK

    • Version: 03-September-2020

    Alternate Names:

    Gene Info:

    Gene Categories:
    CLINICALLY ACTIONABLE

    Publications:

  • CarisMolecularIntelligence: ALK

    • Version: 04-September-2020

    Alternate Names:

    Gene Info:

    Gene Categories:
    CLINICALLY ACTIONABLE

    Publications:

  • FDA: ALK

    • Version: 04-September-2020

    Alternate Names:

    Gene Info:

    Publications:

  • GO: ALK

    • Version: 01-February-2022

    Alternate Names:

    Gene Info:

    Gene Categories:
    TYROSINE KINASE

    Publications:

  • Oncomine: ALK

    • Version: v3

    Alternate Names:

    Gene Info:

    Gene Categories:
    CLINICALLY ACTIONABLE

    Publications:

  • COSMIC: ALK

    • Version: 4-Sep-2020

    Alternate Names:

    Gene Info:

    Gene Categories:
    DRUG RESISTANCE

    Publications:

Disclaimer: This resource is intended for purely research purposes. It should not be used for emergencies or medical or professional advice.

A finding of a drug-gene interaction or potentially druggable category does not necessarily indicate effectiveness (or lack thereof) of any drug or treatment regimen. A finding of no interaction or no potentially druggable category does not necessarily indicate lack of effectiveness of any drug or treatment regimen. Drug-gene interactions or potentially druggable categories are not presented in ranked order of potential or predicted efficacy.

The dgidb.org website does not provide any medical or healthcare products, services or advice, and is not for medical emergencies or urgent situations. IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY, CALL YOUR DOCTOR OR 911 IMMEDIATELY. Information contained on this website is not a substitute for a doctor's medical judgment or advice. We recommend that you discuss your specific, individual health concerns with your doctor or health care professional.

DGIdb (v4.2.0 - sha1 afd9f30b) • Last updated 2020-10-21