title: Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro.
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.
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Mahony
authors.forename: Lynda
authors.initials: L
authors.lastname: Erskine
authors.forename: Jennifer
authors.initials: J
authors.lastname: Niven
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.forename: William Douglas
authors.initials: WD
authors.lastname: Figg
authors.forename: Neil
authors.initials: N
authors.lastname: Vargesson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D000077269:Lenalidomide; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016501:Neurites / Q000378:metabolism*; D009498:Neurotoxins; D013045:Species Specificity; D013723:Teratogens; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology*
chemical_list: D020533:Angiogenesis Inhibitors; D009498:Neurotoxins; D013723:Teratogens; D013792:Thalidomide; C467566:pomalidomide; D000077269:Lenalidomide
keywords: CPS49; Cox2; cytoskeleton; drug screening