PUBLICATION

In vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish embryo and chicken embryo model systems

Authors
Beedie, S.L., Rore, H.M., Barnett, S., Chau, C.H., Luo, W., Greig, N.H., Figg, W.D., Vargesson, N.
ID
ZDB-PUB-160428-1
Date
2016
Source
Oncotarget   7(22): 33237-45 (Journal)
Registered Authors
Keywords
angiogenesis, cancer, inflammation, teratogenesis, thalidomide
MeSH Terms
  • Chick Embryo/drug effects*
  • Animals, Genetically Modified
  • Neovascularization, Physiologic/drug effects
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Neutrophil Infiltration/drug effects
  • High-Throughput Screening Assays*
  • Anti-Inflammatory Agents/pharmacology*
  • Anti-Inflammatory Agents/toxicity
  • Green Fluorescent Proteins/biosynthesis
  • Green Fluorescent Proteins/genetics
  • Risk Assessment
  • Animals
  • Thalidomide/analogs & derivatives
  • Thalidomide/pharmacology*
  • Thalidomide/toxicity
  • Workflow
  • Angiogenesis Inhibitors/pharmacology*
  • Angiogenesis Inhibitors/toxicity
  • Dose-Response Relationship, Drug
  • Drug Discovery/methods*
  • Abnormalities, Drug-Induced/etiology
PubMed
27120781 Full text @ Oncotarget
Abstract
Thalidomide, a drug known for its teratogenic side-effects, is used successfully to treat a variety of clinical conditions including leprosy and multiple myeloma. Intense efforts are underway to synthesize and identify safer, clinically relevant analogs. Here, we conduct a preliminary in vivo screen of a library of new thalidomide analogs to determine which agents demonstrate activity, and describe a cohort of compounds with anti-angiogenic properties, anti-inflammatory properties and some compounds which exhibited both. The combination of the in vivo zebrafish and chicken embryo model systems allows for the accelerated discovery of new, potential therapies for cancerous and inflammatory conditions.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping