In vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish embryo and chicken embryo model systems
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Shaunna L. Beedie1,2, Holly M. Rore1, Shelby Barnett1,4, Cindy H. Chau2, Weiming Luo3, Nigel H. Greig3, William D. Figg2, Neil Vargesson1
1School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK
2Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA
3Drug Design and Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
4Current address: Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester, Manchester, UK
William D. Figg, e-mail: email@example.com
Keywords: angiogenesis, inflammation, thalidomide, cancer, teratogenesis
Received: September 21, 2015 Accepted: March 31, 2016 Published: April 22, 2016
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.
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