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
BE0000359
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

(27 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
Mologni et al., 2015, NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922., Oncotarget
Ceccon et al., 2015, Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma., Mol. Cancer Res.
Katayama et al., 2014, Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib., Clin. Cancer Res.
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.
Lovly et al., 2011, Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors., Cancer Res.
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
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Gambacorti Passerini et al., 2014, Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients., J. Natl. Cancer Inst.
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.
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
Bresler et al., 2011, Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma., Sci Transl Med
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
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.
Ceccon M et al., 2013, Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors., Mol Cancer Res
Katayama et al., 2012, Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers., Sci Transl Med
Kwak et al., 2010, Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer., N. Engl. J. Med.
Lin H et al., 2018, A Novel EML6-ALK FBXO11-ALK Double Fusion Variant in Lung Adenocarcinoma and Response to Crizotinib., 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.
Forde et al., 2012, Crizotinib in the treatment of non-small-cell lung cancer., Expert Opin Pharmacother
Butrynski et al., 2010, Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor., 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
Solomon et al., 2014, First-line crizotinib versus chemotherapy in ALK-positive lung cancer., N. Engl. J. Med.
Schönherr et al., 2011, Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684., Biochem. J.
Peters et al., 2017, Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer., N. Engl. J. 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.
Le et al., 2015, Detection of Crizotinib-Sensitive Lung Adenocarcinomas With MET, ALK, and ROS1 Genomic Alterations via Comprehensive Genomic Profiling., Clin Lung Cancer
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.
Foyil et al., Brentuximab vedotin and crizotinib in anaplastic large-cell lymphoma., Cancer J
Sasaki et al., 2010, The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers., Cancer Res.
Pall G, 2015, The next-generation ALK inhibitors., Curr Opin Oncol
Wiesner et al., 2015, Alternative transcription initiation leads to expression of a novel ALK isoform in cancer., Nature
Ehmann F et al., 2014, European Medicines Agency initiatives and perspectives on pharmacogenomics., Br J Clin Pharmacol
Mossé et al., 2008, Identification of ALK as a major familial neuroblastoma predisposition gene., Nature
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.
Morán et al., 2013, Targeting EML4-ALK driven non-small cell lung cancer (NSCLC)., Transl Lung Cancer Res
Orimo et al., 1990, [The role of hyperlipidemia in the development of atherosclerosis]., Nippon Rinsho
George et al., 2008, Activating mutations in ALK provide a therapeutic target in neuroblastoma., Nature
Godbert et al., 2015, Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase-Rearranged Anaplastic Thyroid Carcinoma., J. Clin. Oncol.
Gainor et al., 2016, Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer., Cancer Discov
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.
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
2015, Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer., N. Engl. J. Med.
Gambacorti-Passerini et al., 2011, Crizotinib in anaplastic large-cell lymphoma., N. Engl. J. Med.
Sakamoto et al., 2011, CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant., Cancer Cell
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.
Choi et al., 2010, EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors., N. Engl. J. Med.
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
Janoueix-Lerosey et al., 2008, Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma., Nature
Shaw et al., 2016, Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F., N. Engl. J. Med.
Krytska et al., 2016, Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma., Clin. Cancer Res.
Heuckmann et al., 2011, ALK mutations conferring differential resistance to structurally diverse ALK inhibitors., Clin. Cancer Res.
Shaw et al., 2014, Ceritinib in ALK-rearranged non-small-cell lung cancer., N. Engl. J. Med.
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
Shaw et al., 2013, Crizotinib versus chemotherapy in advanced ALK-positive lung cancer., N. Engl. J. Med.
Kanaan Z et al., 2015, Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond., Onco Targets Ther
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
Gainor et al., 2015, Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib., Clin. Cancer Res.
Kim et al., 2013, Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer., J Thorac Oncol
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.
Sasaki et al., 2011, A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors., Cancer Res.
Mazot et al., 2011, The constitutive activity of the ALK mutated at positions F1174 or R1275 impairs receptor trafficking., Oncogene
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.
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.
Friboulet et al., 2014, The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer., Cancer Discov
Chung et al., 2014, A Poorly Differentiated Malignant Neoplasm Lacking Lung Markers Harbors an EML4-ALK Rearrangement and Responds to Crizotinib., Case Rep Oncol
Paik J et al., 2018, Alectinib: A Review in Advanced, ALK-Positive NSCLC., Drugs
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
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
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
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
Shaw et al., 2016, Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial., Lancet Oncol.
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., 2016, Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study., J. Clin. 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.
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
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
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.
Crystal et al., 2014, Patient-derived models of acquired resistance can identify effective drug combinations for cancer., Science
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.
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.
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
Zou et al., 2015, PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models., Cancer Cell
Ardini et al., 2016, Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications., Mol. Cancer Ther.
Amatu et al., 2015, Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer., Br. J. Cancer
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
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
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.
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
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.
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.
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
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
Galkin et al., 2007, Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK., Proc. Natl. Acad. Sci. U.S.A.
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.
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.
Markham A, 2017, Brigatinib: First Global Approval., Drugs
Iragavarapu C et al., 2015, Novel ALK inhibitors in clinical use and development., J Hematol Oncol
Siaw et al., 2016, Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice., Oncotarget
Wu et al., 2016, Second- and third-generation ALK inhibitors for non-small cell lung cancer., J Hematol Oncol
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.
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.
Solomon et al., 2014, Current status of targeted therapy for anaplastic lymphoma kinase-rearranged non-small cell lung cancer., Clin. Pharmacol. Ther.
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
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
Thom C, 2015, Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients., Future 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
Rolf MG et al., 2015, In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib., Pharmacol Res Perspect
Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov
Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

ALECTINIB ALK

Interaction Score: 4.69

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:I1171T

Drug family ALK inhibitor

Alteration ALK__.

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

Sources:
OncoKB FDA PharmGKB JAX-CKB CIViC TTD DrugBank COSMIC TALC MyCancerGenome GuideToPharmacology CGI
CRIZOTINIB ALK

Interaction Score: 4.0

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:C1156Y,L1196M

Alteration ALK:L1198F

Alteration ALK:F856S,A348D

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

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

Interaction Score: 3.93

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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

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

Interaction Score: 3.53

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:
26438117 21613408 31628085

Sources:
CancerCommons JAX-CKB CIViC TTD TALC MyCancerGenome GuideToPharmacology ChemblInteractions
CHEMBL3397300 ALK

Interaction Score: 2.73

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Indication/Tumor Type Advanced Solid Tumor

Response Type decreased response

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

Sources:
MyCancerGenomeClinicalTrial JAX-CKB TTD TALC MyCancerGenome
LORLATINIB ALK

Interaction Score: 2.34

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Approval Status Preclinical - Cell line xenograft

Response Type conflicting

Indication/Tumor Type lung cancer

PMIDs:
25749034 30413378 27432227 26698910 29650534 26144315 26554404 28285684

Sources:
OncoKB FDA PharmGKB JAX-CKB CIViC TTD DrugBank COSMIC GuideToPharmacology
ASP-3026 ALK

Interaction Score: 2.17

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Lung

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

PMIDs:
27009859 25749034 25421750 25228534

Sources:
CancerCommons JAX-CKB TTD MyCancerGenome ChemblInteractions
BRIGATINIB ALK

Interaction Score: 1.83

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Wild type ALK

Direct Interaction? True

Endogenous Drug? False

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

Sources:
OncoKB FDA PharmGKB CIViC TTD DrugBank COSMIC GuideToPharmacology ChemblInteractions
CHEMBL473773 ALK

Interaction Score: 0.96

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17625570

Sources:
CIViC
CEP-37440 ALK

Interaction Score: 0.96

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction? False

Endogenous Drug? False

Specific Action of the Ligand Inhibition

PMIDs:
None found

Sources:
GuideToPharmacology ChemblInteractions
DALANTERCEPT ALK

Interaction Score: 0.72

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dalantercept + Cisplatin

Indication/Tumor Type breast cancer

Response Type predicted – sensitive

PMIDs:
25888978 26373572

Sources:
JAX-CKB
GILTERITINIB ALK

Interaction Score: 0.53

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
27775694 28516360 26279055

Sources:
DrugBank GuideToPharmacology
LUMINESPIB ALK

Interaction Score: 0.48

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26698910

Sources:
CIViC
ALECTINIB HYDROCHLORIDE ALK

Interaction Score: 0.48

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: 0.39

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15920698

Sources:
NCI
DURVALUMAB ALK

Interaction Score: 0.32

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: 0.32

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: 0.3

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Clinical Study

Response Type decreased response

PMIDs:
27225694

Sources:
FDA PharmGKB JAX-CKB
NIVOLUMAB ALK

Interaction Score: 0.26

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Clinical Study

Response Type decreased response

PMIDs:
27225694

Sources:
FDA PharmGKB JAX-CKB
PEMBROLIZUMAB ALK

Interaction Score: 0.18

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:
FDA PharmGKB JAX-CKB
REPOTRECTINIB ALK

Interaction Score: 0.16

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: 0.16

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
SARACATINIB ALK

Interaction Score: 0.15

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: 0.14

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
21642865

Sources:
CIViC
TOPOTECAN ALK

Interaction Score: 0.13

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: 0.12

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
GANETESPIB ALK

Interaction Score: 0.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
MyCancerGenomeClinicalTrial
ENTRECTINIB ALK

Interaction Score: 0.1

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type colorectal cancer

Response Type resistant

Approval Status Preclinical

PMIDs:
26939704 26633560 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: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dalantercept + Doxorubicin

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
16880530 26373572 28455243

Sources:
NCI JAX-CKB
ADENOSINE TRIPHOSPHATE ALK

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
17139284 17016423

Sources:
DrugBank
TAK-715 ALK

Interaction Score: 0.04

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: 0.02

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: 0.02

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
19035792

Sources:
DTC
CHEMBL1997335 ALK

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
OSI-632 ALK

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CHEMBL379975 ALK

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
PAZOPANIB ALK

Interaction Score: 0.02

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: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
TOZASERTIB ALK

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
LINIFANIB ALK

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
CISPLATIN ALK

Interaction Score: 0.01

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
FOSTAMATINIB ALK

Interaction Score: 0.01

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

PMIDs:
26516587

Sources:
DrugBank

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

DrugBank: BE0000359

Version: 5.1.7

Alternate Names:

ALK DrugBank Gene Name

Q9UM73 UniProt Accession

238 Entrez Gene Id

Gene Info:

Publications:

Overington et al., 2006, How many drug targets are there?, Nat Rev Drug Discov

Imming et al., 2006, Drugs, their targets and the nature and number of drug targets., Nat Rev Drug Discov

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.

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:
Pharos: ALK
- Version: 03-September-2020
Alternate Names:

ALK tyrosine kinase receptor Gene Name

Q9UM73 UniProt ID

Gene Info:

Gene Categories:

KINASE

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:
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: 05-September-2020
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:

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

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

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

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

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

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

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

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

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: 26438117 21613408 31628085

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

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

Sources: MyCancerGenomeClinicalTrial JAX-CKB TTD TALC MyCancerGenome

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 25749034 30413378 27432227 26698910 29650534 26144315 26554404 28285684

Sources: OncoKB FDA PharmGKB JAX-CKB CIViC TTD DrugBank COSMIC GuideToPharmacology

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 27009859 25749034 25421750 25228534

Sources: CancerCommons JAX-CKB TTD MyCancerGenome ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

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

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

Sources: OncoKB FDA PharmGKB CIViC TTD DrugBank COSMIC GuideToPharmacology ChemblInteractions

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: GuideToPharmacology ChemblInteractions

Interaction Types & Directionality: n/a

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

PMIDs: 25888978 26373572

Sources: JAX-CKB

Interaction Types & Directionality: inhibitor (inhibitory)

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

PMIDs: 27775694 28516360 26279055

Sources: DrugBank 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: FDA PharmGKB JAX-CKB

Interaction Types & Directionality: n/a

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

PMIDs: 27225694

Sources: FDA PharmGKB JAX-CKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:I1171T

Drug family ALK inhibitor

Alteration ALK__.

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

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Alteration ALK:C1156Y,L1196M

Alteration ALK:L1198F

Alteration ALK:F856S,A348D

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

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? True

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

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:
26438117 21613408 31628085

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

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Notes

Indication/Tumor Type Advanced Solid Tumor

Response Type decreased response

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

Sources:
MyCancerGenomeClinicalTrial JAX-CKB TTD TALC MyCancerGenome

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Approval Status Preclinical - Cell line xenograft

Response Type conflicting

Indication/Tumor Type lung cancer

PMIDs:
25749034 30413378 27432227 26698910 29650534 26144315 26554404 28285684

Sources:
OncoKB FDA PharmGKB JAX-CKB CIViC TTD DrugBank COSMIC GuideToPharmacology

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Reported Cancer Type Lung

Indication/Tumor Type Advanced Solid Tumor

Response Type resistant

PMIDs:
27009859 25749034 25421750 25228534

Sources:
CancerCommons JAX-CKB TTD MyCancerGenome ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Details of the Assay for Interaction Wild type ALK

Direct Interaction? True

Endogenous Drug? False

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

Sources:
OncoKB FDA PharmGKB CIViC TTD DrugBank COSMIC GuideToPharmacology ChemblInteractions

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:
GuideToPharmacology ChemblInteractions

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dalantercept + Cisplatin

Indication/Tumor Type breast cancer

Response Type predicted – sensitive

PMIDs:
25888978 26373572

Sources:
JAX-CKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Specific Action of the Ligand Inhibition

Endogenous Drug? False

Direct Interaction? False

PMIDs:
27775694 28516360 26279055

Sources:
DrugBank 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:
FDA PharmGKB JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Clinical Study

Response Type decreased response

PMIDs:
27225694

Sources:
FDA PharmGKB JAX-CKB

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:
FDA PharmGKB JAX-CKB

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

ALK	DrugBank Gene Name
Q9UM73	UniProt Accession
238	Entrez Gene Id

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