In vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish embryo and chicken embryo model systems.
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.
School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.|Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA.
Shaunna L
SL
Beedie
School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
Holly M
HM
Rore
School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.|Current address: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Manchester, UK.
Shelby
S
Barnett
Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA.
Cindy H
CH
Chau
Drug Design and Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Weiming
W
Luo
Drug Design and Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Nigel H
NH
Greig
Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA.
William D
WD
Figg
School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
Neil
N
Vargesson
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D030801:Animals, Genetically Modified; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D002642:Chick Embryo / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D057166:High-Throughput Screening Assays; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D018570:Risk Assessment; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D057188:Workflow; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013792:Thalidomide
angiogenesis; cancer; inflammation; teratogenesis; thalidomide