DGIdb - ALK Gene Record

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
1839
NP_004295
Q9UM73
NM_004304
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

Gene Info:

GuideToPharmacology Gene Category Name	Type XIX RTKs: Leukocyte tyrosine kinase (LTK) receptor family
GuideToPharmacology Gene Category ID	329
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

(26 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
Antar A et al., 2017, Inhibition of FLT3 in AML: a focus on sorafenib., Bone Marrow Transplant
Thom C, 2015, Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients., Future Oncol
Mori M et al., 2017, Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia., Invest New Drugs
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

ALECTINIB ALK

Interaction Score: 5.32

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:I1171T

Drug family ALK inhibitor

Alteration ALK__.

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 CGI COSMIC CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB
CRIZOTINIB ALK

Interaction Score: 4.59

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 MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions CGI DoCM COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB
CERITINIB ALK

Interaction Score: 4.48

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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 CGI DoCM COSMIC CIViC GuideToPharmacology CancerCommons MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB
ENSARTINIB ALK

Interaction Score: 4.1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Details of the Assay for Interaction Result from DiscoveRx KINOMEscan® selectivity screen.

Specific Action of the Ligand Inhibition

PMIDs:
21613408 26438117 31628085

Sources:
TALC MyCancerGenome JAX-CKB ChemblInteractions CIViC GuideToPharmacology CancerCommons TTD
BRIGATINIB ALK

Interaction Score: 4.03

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Wild type ALK

Direct Interaction? True

Endogenous Drug? False

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

Sources:
ChemblInteractions COSMIC CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB
CHEMBL3397300 ALK

Interaction Score: 3.17

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: 2.56

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 GuideToPharmacology PharmGKB TTD FDA OncoKB
ASP-3026 ALK

Interaction Score: 2.52

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: 1.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17625570

Sources:
CIViC
CEP-37440 ALK

Interaction Score: 1.12

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
ChemblInteractions GuideToPharmacology
DALANTERCEPT ALK

Interaction Score: 0.84

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
GILTERITINIB ALK

Interaction Score: 0.56

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
27775694 26279055 28516360

Sources:
GuideToPharmacology
LUMINESPIB ALK

Interaction Score: 0.56

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26698910

Sources:
CIViC
ALECTINIB HYDROCHLORIDE ALK

Interaction Score: 0.56

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction ALK tyrosine kinase receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
INTERLEUKIN-10 ALK

Interaction Score: 0.45

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15920698

Sources:
NCI
DURVALUMAB ALK

Interaction Score: 0.37

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
ONALESPIB ALK

Interaction Score: 0.37

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
ATEZOLIZUMAB ALK

Interaction Score: 0.34

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: 0.3

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: 0.2

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
REPOTRECTINIB ALK

Interaction Score: 0.19

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Details of Interaction IC<sub>50</sub> for ALK<sup>G1202R</sup> is 1.2 nM.

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology
RAMUCIRUMAB ALK

Interaction Score: 0.19

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
SARACATINIB ALK

Interaction Score: 0.17

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
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
CRENOLANIB ALK

Interaction Score: 0.14

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
GANETESPIB ALK

Interaction Score: 0.12

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
ENTRECTINIB ALK

Interaction Score: 0.11

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: 0.06

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
CHEMBL546797 ALK

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
IMATINIB ALK

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16970400

Sources:
NCI
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: 0.02

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
CEDIRANIB 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
JNJ-7706621 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
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
TOZASERTIB 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
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
TAE-684 ALK

Interaction Score: 0.01

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

PMIDs:
None found

Sources:
GuideToPharmacology
PF-00562271 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
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:

GuideToPharmacology: 238
- Version: 29-September-2020
Alternate Names:

427 HUGO Gene ID

427 HUGO Gene Symbol

ALK receptor tyrosine kinase HUGO Gene Name

Gene Info:

GuideToPharmacology Gene Category Name Type XIX RTKs: Leukocyte tyrosine kinase (LTK) receptor family

GuideToPharmacology Gene Category ID 329

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

CGI: ALK

Version: 27-September-2017

Alternate Names:

Gene Info:

Publications:

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

Katayama et al., 2012, Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers., Sci Transl Med

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

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-May-2021
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:
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:
GO: ALK
- Version: 01-May-2021
Alternate Names:

Gene Info:

Gene Categories:

TYROSINE KINASE

Publications:

Alteration	ALK:I1171T
Drug family	ALK inhibitor
Alteration	ALK__.

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

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

Notes
Details of the Assay for Interaction	Result from DiscoveRx KINOMEscan® selectivity screen.
Specific Action of the Ligand	Inhibition

Details of the Assay for Interaction	Wild type ALK
Direct Interaction?	True
Endogenous Drug?	False

Notes
Indication/Tumor Type	Advanced Solid Tumor
Response Type	decreased response

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

Reported Cancer Type	Lung
Indication/Tumor Type	Advanced Solid Tumor
Response Type	resistant

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

Mechanism of Interaction	ALK tyrosine kinase receptor inhibitor
Direct Interaction	yes

antagonist (inhibitory)
inhibitor (inhibitory)

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

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

Evidence Type	Actionable
Approval Status	Clinical Study
Response Type	decreased response

Specific Action of the Ligand	Inhibition
Details of Interaction	IC<sub>50</sub> for ALK<sup>G1202R</sup> is 1.2 nM.
Endogenous Drug?	False

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

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

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

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

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

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

ALK Gene Record

ALK 238 Druggable GenomeClinically ActionableDrug Resistance

Alternate Names:

Gene Info:

Gene Categories: Category Details

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Alteration ALK:I1171T Drug family ALK inhibitor Alteration ALK__.

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 CGI COSMIC CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB

Interaction Types & Directionality: inhibitor (inhibitory)

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

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

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

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Notes Details of the Assay for Interaction Result from DiscoveRx KINOMEscan&reg; selectivity screen. Specific Action of the Ligand Inhibition

PMIDs: 21613408 26438117 31628085

Sources: TALC MyCancerGenome JAX-CKB ChemblInteractions CIViC GuideToPharmacology CancerCommons TTD

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Details of the Assay for Interaction Wild type ALK Direct Interaction? True Endogenous Drug? False

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

Sources: ChemblInteractions COSMIC CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB

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

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 GuideToPharmacology PharmGKB TTD FDA OncoKB

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

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 17625570

Sources: CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: None found

Sources: ChemblInteractions GuideToPharmacology

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 27775694 26279055 28516360

Sources: GuideToPharmacology

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 26698910

Sources: CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15920698

Sources: NCI

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

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

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

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:I1171T

Drug family ALK inhibitor

Alteration ALK__.

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 CGI COSMIC CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:C1156Y,L1196M

Alteration ALK:L1198F

Alteration ALK:F856S,A348D

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

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Details of the Assay for Interaction Result from DiscoveRx KINOMEscan® selectivity screen.

Specific Action of the Ligand Inhibition

PMIDs:
21613408 26438117 31628085

Sources:
TALC MyCancerGenome JAX-CKB ChemblInteractions CIViC GuideToPharmacology CancerCommons TTD

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Wild type ALK

Direct Interaction? True

Endogenous Drug? False

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

Sources:
ChemblInteractions COSMIC CIViC GuideToPharmacology PharmGKB TTD FDA OncoKB

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

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 GuideToPharmacology PharmGKB TTD FDA OncoKB

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

Interaction Types & Directionality:

n/a

PMIDs:
17625570

Sources:
CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
ChemblInteractions GuideToPharmacology

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
27775694 26279055 28516360

Sources:
GuideToPharmacology

Interaction Types & Directionality:

n/a

PMIDs:
26698910

Sources:
CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction ALK tyrosine kinase receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

n/a

PMIDs:
15920698

Sources:
NCI

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

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

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

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

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Details of Interaction IC<sub>50</sub> for ALK<sup>G1202R</sup> is 1.2 nM.

Endogenous Drug? False

PMIDs:
None found

Sources:
GuideToPharmacology

Interaction Types & Directionality:

n/a

427	HUGO Gene ID
427	HUGO Gene Symbol
ALK receptor tyrosine kinase	HUGO Gene Name

238	Entrez Gene Id
ALK	MyCancerGenome Gene Symbol
ALK	MyCancerGenome Reported Gene Name

ALK	GENE_SYMBOL
ALK tyrosine kinase receptor	UNIPROT
Anaplastic lymphoma kinase	UNIPROT

238	OncoKB Entrez Id
NBLST3	OncoKB Gene Synonym
CD246	OncoKB Gene Synonym