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
  • Abnormalities, Drug-Induced/etiology
  • Angiogenesis Inhibitors/pharmacology*
  • Angiogenesis Inhibitors/toxicity
  • Animals
  • Animals, Genetically Modified
  • Anti-Inflammatory Agents/pharmacology*
  • Anti-Inflammatory Agents/toxicity
  • Chick Embryo/drug effects*
  • Dose-Response Relationship, Drug
  • Drug Discovery/methods*
  • Green Fluorescent Proteins/biosynthesis
  • Green Fluorescent Proteins/genetics
  • High-Throughput Screening Assays*
  • Neovascularization, Physiologic/drug effects
  • Neutrophil Infiltration/drug effects
  • Risk Assessment
  • Thalidomide/analogs & derivatives
  • Thalidomide/pharmacology*
  • Thalidomide/toxicity
  • Workflow
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
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