Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro.

C Mahony, L Erskine, J Niven, NH Greig, WD Figg, N Vargesson

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently.
Original languageEnglish
Pages (from-to)12703-12708
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number31
DOIs
Publication statusPublished - Jul 2013

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