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

Chris Mahony, Lynda Erskine, Jennifer Niven, Nigel H Greig, William Douglas Figg, Neil Vargesson (Corresponding Author)

Research output: Contribution to journalArticle

34 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
Number of pages6
JournalPNAS
Volume110
Issue number31
Early online date15 Jul 2013
DOIs
Publication statusPublished - 30 Jul 2013

Keywords

  • thalidomide
  • pomalidomide
  • lenalidomide
  • angiogenesis
  • inflammation
  • cytoskeleton
  • chick embryo
  • zebrafish embryo
  • CPS49
  • cox2
  • drug screening

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