Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish.

Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Research Abstract Details 

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Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Abstract Text:

T Cameron Tran,Blossom Sneed,Jamil Haider,Delali Blavo,Audrey White,Temitope Aiyejorun,Timothy C Baranowski,Amy L Rubinstein,Thanh N Doan,Raymond Dingledine,Eric M Sandberg,T Cameron Tran,Blossom Sneed,Jamil Haider,Delali Blavo,Audrey White,Temitope Aiyejorun,Timothy C Baranowski,Amy L Rubinstein,Thanh N Doan,Raymond Dingledine,Eric M Sandberg,

Pathologic angiogenesis has emerged as an important therapeutic target in several major diseases. Zebrafish offer the potential for high-throughput drug discovery in a whole vertebrate system. We developed the first quantitative, automated assay for antiangiogenic compound identification using zebrafish embryos. This assay uses transgenic zebrafish with fluorescent blood vessels to facilitate image analysis. We developed methods for automated drugging and imaging of zebrafish in 384-well plates and developed a custom algorithm to quantify the number of angiogenic blood vessels in zebrafish. The assay was used to screen the LOPAC1280 compound library for antiangiogenic compounds. Two known antiangiogenic compounds, SU4312 and AG1478, were identified as hits. Additionally, one compound with no previously known antiangiogenic activity, indirubin-3'-monoxime (IRO), was identified. We showed that each of the hit compounds had dose-dependent antiangiogenic activity in zebrafish. The IC(50) of SU4312, AG1478, and IRO in the zebrafish angiogenesis assay was 1.8, 8.5, and 0.31 micromol/L, respectively. IRO had the highest potency of the hit compounds. Moreover, IRO inhibited human umbilical vein endothelial cell tube formation and proliferation (IC(50) of 6.5 and 0.36 micromol/L, respectively). It is therefore the first antiangiogenic compound discovered initially in a zebrafish assay that also has demonstrable activity in human endothelial cell-based angiogenesis assays.

Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Publishing Authors By Initials

TC Tran,B Sneed,J Haider,D Blavo,A White,T Aiyejorun,TC Baranowski,AL Rubinstein,TN Doan,R Dingledine,EM Sandberg,TC Tran,B Sneed,J Haider,D Blavo,A White,T Aiyejorun,TC Baranowski,AL Rubinstein,TN Doan,R Dingledine,EM Sandberg,

For similar animals: chordata: vertebrates: fishes: cypriniformes: cyprinidae: zebrafish research abstracts see: animals: chordata: vertebrates: fishes: cypriniformes: cyprinidae: zebrafish research

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Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cancer research

VOLUME: 67

Page Numbers: 11386-92

Journal Abbreviation: Cancer Res.

ISSN: 1538-7445

DAY: 1

MONTH: Dec

YEAR: 2007

Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Keywords Mesh Terms:

KEYWORDS: Zebrafish

MESH TERMS: metabolism

Chemical & Substance for Abstract: Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Information

Substance Name: Thymidine

Registry Number: 50-89-5

Grant and Affiliation Information for Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish.

AFFILIATION: Zygogen, LLC, 24 Peachtree Center Avenue, 520 Kell Hall, Atlanta, GA 30303, USA.

Country: United States

AGENCY: United States NHGRI

GRANT: U54 HG003918

ACRONYM: HG

MEDLINETA: Cancer Res

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