Reactome | Liganded-ALK dimer binds type I ALK-binding TKIs

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Liganded-ALK dimer binds type I ALK-binding TKIs Show undefined attributes

authored	[InstanceEdit:9725664] Rothfels, Karen, 2021-03-30
category	binding
compartment	[Compartment:70101] cytosol [Compartment:876] plasma membrane
created	[InstanceEdit:9700663] Rothfels, Karen, 2020-09-16
dbId	9700662
diseaseReaction	[FailedReaction:R-HSA-9700658] ceritinib-resistant ALK mutants don't bind ceritinib - Homo sapiens [FailedReaction:R-HSA-9715357] crizotinib-resistant ALK mutants don't bind crizotinib - Homo sapiens [FailedReaction:R-HSA-9715355] lorlatinib-resistant ALK mutants don't bind lorlatinib - Homo sapiens [FailedReaction:R-HSA-9700646] ASP-3026- resistant ALK mutants don't bind ASP-3026 - Homo sapiens [Reaction:R-HSA-9700131] ALK mutants bind type I TKIs - Homo sapiens [FailedReaction:R-HSA-9700656] alectinib resistant ALK mutants don't bind alectinib - Homo sapiens [FailedReaction:R-HSA-9700114] NVP-TAE684-resistant ALK mutants don't bind NVP-TAE684 - Homo sapiens [FailedReaction:R-HSA-9715356] brigatinib-resistant ALK mutants don't bind brigatinib - Homo sapiens
displayName	Liganded-ALK dimer binds type I ALK-binding TKIs
edited	[InstanceEdit:9725664] Rothfels, Karen, 2021-03-30
eventOf	[Pathway:R-HSA-201556] Signaling by ALK - Homo sapiens
input	[CandidateSet:R-HSA-9850908] ligand-bound ALK dimer [plasma membrane] [DefinedSet:R-ALL-9699973] type I ALK-binding TKIs [cytosol]
isChimeric	false
isInDisease	false
isInferred	false
literatureReference	[LiteratureReference:9671447] Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases [LiteratureReference:9699633] Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition [LiteratureReference:9702247] Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases [LiteratureReference:9702250] Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond [LiteratureReference:9702256] Crizotinib in anaplastic large-cell lymphoma [LiteratureReference:9702293] Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib [LiteratureReference:9700317] ALK F1174V mutation confers sensitivity while ALK I1171 mutation confers resistance to alectinib. The importance of serial biopsy post progression [LiteratureReference:9702216] Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial [LiteratureReference:9700339] Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors [LiteratureReference:9700357] Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma [LiteratureReference:9702309] The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models [LiteratureReference:9702243] Ceritinib in ALK-rearranged non-small-cell lung cancer [LiteratureReference:9702281] Diverse Resistance Mechanisms to the Third-Generation ALK Inhibitor Lorlatinib in ALK-Rearranged Lung Cancer [LiteratureReference:9699697] Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK [LiteratureReference:9699768] Role and targeting of anaplastic lymphoma kinase in cancer [LiteratureReference:9843068] The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status [LiteratureReference:9843025] IL10RA modulates crizotinib sensitivity in NPM1-ALK+ anaplastic large cell lymphoma [LiteratureReference:9717312] Targeting ALK: Precision Medicine Takes on Drug Resistance
maxDepth	1
modified	[InstanceEdit:10732209] Weiser, Joel, 2026-03-16
name	Liganded-ALK dimer binds type I ALK-binding TKIs
orthologousEvent	[Reaction:R-MMU-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Mus musculus [Reaction:R-RNO-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Rattus norvegicus [Reaction:R-CFA-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Canis familiaris [Reaction:R-BTA-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Bos taurus [Reaction:R-SSC-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Sus scrofa [Reaction:R-DRE-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Danio rerio [Reaction:R-XTR-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Xenopus tropicalis [Reaction:R-GGA-9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - Gallus gallus
output	[Complex:R-HSA-9700592] ALK dimer:ligand:type I ALK binding TKI [plasma membrane]
precedingEvent	[Reaction:R-HSA-9842656] ALK binds ALKAL ligand - Homo sapiens [Reaction:R-HSA-9667914] ALK binds ligand midkine (MDK) - Homo sapiens [Reaction:R-HSA-201486] ALK binds ligand pleiotrophin (PTN) - Homo sapiens
previousReviewStatus	[ReviewStatus:9821384] two stars
releaseDate	2021-06-09
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:9729891] Inghirami, Giorgio, 2021-05-04 [InstanceEdit:9852935] Turner, Suzanne, 2023-11-08
schemaClass	Reaction
species	[Species:48887] Homo sapiens
stId	R-HSA-9700662
summation	[Summation:9702326] ALK can be bound and inhibited by type I tyrosine kinase inh...
updateTrackers	[UpdateTracker:9853239] Update Tracker - [Reaction:9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - v87:[addLiteratureReference, add_removeInput, modifyText]

Referrals

(hasEvent)	[Pathway:R-HSA-201556] Signaling by ALK
(normalReaction)	[FailedReaction:R-HSA-9700658] ceritinib-resistant ALK mutants don't bind ceritinib [FailedReaction:R-HSA-9715357] crizotinib-resistant ALK mutants don't bind crizotinib [FailedReaction:R-HSA-9715355] lorlatinib-resistant ALK mutants don't bind lorlatinib [FailedReaction:R-HSA-9700646] ASP-3026- resistant ALK mutants don't bind ASP-3026 [Reaction:R-HSA-9700131] ALK mutants bind type I TKIs [FailedReaction:R-HSA-9700656] alectinib resistant ALK mutants don't bind alectinib [FailedReaction:R-HSA-9700114] NVP-TAE684-resistant ALK mutants don't bind NVP-TAE684 [FailedReaction:R-HSA-9715356] brigatinib-resistant ALK mutants don't bind brigatinib
(updatedInstance)	[UpdateTracker:9853239] Update Tracker - [Reaction:9700662] Liganded-ALK dimer binds type I ALK-binding TKIs - v87:[addLiteratureReference, add_removeInput, modifyText]

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