A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors

Frederico S L M Rodrigues, Xueyan Yang, Masataka Nikaido, Qingsong Liu, Robert N Kelsh

Research output: Contribution to journalArticle

  • 5 Citations

Abstract

Anaplastic lymphoma kinase (ALK) is an important drug target in many cancers, including lymphoma, neuroblastoma, and lung cancer. Here, we demonstrate proof-of-principle for a novel and inexpensive assay for ALK inhibitor activity and identification in zebrafish. We demonstrate that the human oncogenic ALK fusion, NPM-ALK, drives overproduction of iridophores, a highly visible, shiny pigment cell-type in zebrafish. Treatment with the potent ALK inhibitor, TAE684, fully inhibits production of ALK-dependent iridophores. Using our assay, we test multiple properties of TAE684 in vivo, including efficacy, specificity, and toxicity. We note that TAE684 also inhibits the closely related leukocyte tyrosine kinase (Ltk) that is required for endogenous iridophore development. Similar effects are observed with an independent inhibitor, Crizotinib. Our assay can thus be utilized to identify ALK or LTK inhibitors. Importantly, the natural reflectivity of iridophores lends itself to automation for high throughput assessment of ALK and LTK inhibitor compounds in vivo.
LanguageEnglish
Pages1968-1974
Number of pages7
JournalACS Chemical Biology
Volume7
Issue number12
Early online date16 Sep 2012
DOIs
StatusPublished - 21 Dec 2012

Fingerprint

Assays
Zebrafish
anaplastic lymphoma kinase
Automation
Neuroblastoma
Pigments
Protein-Tyrosine Kinases
Toxicity
Lymphoma
Lung Neoplasms
Leukocytes
Fusion reactions
Throughput
Pharmaceutical Preparations
NVP-TAE684
Neoplasms
crizotinib

Cite this

A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors. / Rodrigues, Frederico S L M; Yang, Xueyan; Nikaido, Masataka; Liu, Qingsong; Kelsh, Robert N.

In: ACS Chemical Biology, Vol. 7, No. 12, 21.12.2012, p. 1968-1974.

Research output: Contribution to journalArticle

Rodrigues, FSLM, Yang, X, Nikaido, M, Liu, Q & Kelsh, RN 2012, 'A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors' ACS Chemical Biology, vol. 7, no. 12, pp. 1968-1974. DOI: 10.1021/cb300361a
Rodrigues FSLM, Yang X, Nikaido M, Liu Q, Kelsh RN. A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors. ACS Chemical Biology. 2012 Dec 21;7(12):1968-1974. Available from, DOI: 10.1021/cb300361a
Rodrigues, Frederico S L M ; Yang, Xueyan ; Nikaido, Masataka ; Liu, Qingsong ; Kelsh, Robert N. / A simple, highly visual in vivo screen for anaplastic lymphoma kinase inhibitors. In: ACS Chemical Biology. 2012 ; Vol. 7, No. 12. pp. 1968-1974
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