Teratogenic effects of thalidomide: molecular mechanisms

  title={Teratogenic effects of thalidomide: molecular mechanisms},
  author={Takumi Ito and Hideki Ando and Hiroshi Handa},
  journal={Cellular and Molecular Life Sciences},
Fifty years ago, prescription of the sedative thalidomide caused a worldwide epidemic of multiple birth defects. The drug is now used in the treatment of leprosy and multiple myeloma. However, its use is limited due to its potent teratogenic activity. The mechanism by which thalidomide causes limb malformations and other developmental defects is a long-standing question. Multiple hypotheses exist to explain the molecular mechanism of thalidomide action. Among them, theories involving oxidative… 

Molecular Mechanisms of the Teratogenic Effects of Thalidomide

The current understanding of molecular mechanisms of thalidomide, particularly in the context of its teratogenicity, is described.

Molecular Mechanisms of Thalidomide-induced Limb Malformations

It looks like that thalidomide embryopathy is a multifactorial event and further studies are needed to clarify the possible interactions involving different pathways, and several pathways including increased oxidative stress, impairing nuclear factor-kB activity, fibroblast growth factor 10 and fibro Blast growth factor 8 downregulation have been widely proposed.

Thalidomide‐induced teratogenesis: History and mechanisms

  • N. Vargesson
  • Medicine
    Birth defects research. Part C, Embryo today : reviews
  • 2015
The history of thalidomide, the range and type of damage the drug caused, and the mechanisms of action the drug uses including recent molecular advances and new findings are looked at.

Thalidomide Analogs in Brazil: Concern About Teratogenesis

It has been more than 50 years since thalidomide was withdrawn from the world market due to its teratogenic potential. However, its widespread use around the world resumed due to its

Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs

An overview of the current understanding of mechanism of action of IMiDs via CRBN and prospects for the development of new drugs that degrade protein of interest is given.

Thalidomide Embryopathy: An Enigmatic Challenge

The purpose of this review is to look at the recent work carried out into understanding how thalidomide causes birth defects, it’s molecular targets and the challenges that remain to be elucidated.

Therapeutic effects of thalidomide in hematologic disorders: a review

Thalidomide's therapeutic effects in hematology is reviewed, including those on multiple myeloma, Waldenstroem macroglobulinemia, lymphomas, mantle-cell lymphoma, myelodysplastic syndrome, hereditary hemorrhagic telangiectasia, and graftversus-host disease.

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate

It is shown that thalidomide is not teratogenic in transgenic mice expressing human cereblon, indicating that binding to Cereblon is not sufficient to cause birth defects, and SALL4 is identified as a thalidmide-dependent cereBlon neosubstrate.

Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy

It is anticipated that elucidation of important IMiD targets will allow the rational development of new-generation therapeutics with the potential to separate thalidomide-analogue efficacy from clinical toxicity, as well as define the molecular IMid targets and biological outputs that underpin their anti-neoplastic activity.



Identification of a Primary Target of Thalidomide Teratogenicity

A basis for thalidomide teratogenicity is revealed and may contribute to the development of new thalidmide derivatives without teratogenic activity.

Thalidomide resistance is based on the capacity of the glutathione-dependent antioxidant defense.

Thalidomide-resistance is based on the capacity of the glutathione-dependent antioxidant defense and substantial differences between human and mouse embryonic cells regarding the protection against oxidative stress are described.

Mechanism of action in thalidomide teratogenesis.

Thalidomide is an inhibitor of angiogenesis.

Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature ofThalidomid-treated embryos, which shed light on the mechanism of the teratogenicity of the drug.

The thalidomide saga.

A novel hypothesis for thalidomide-induced limb teratogenesis: redox misregulation of the NF-kappaB pathway.

It is hypothesized that species-selective alterations in redox microenvironment caused by free radical production from thalidomide results in attenuation of the NF-kappaB-mediated gene expression that is responsible for limb outgrowth.

New cases of thalidomide embryopathy in Brazil.

It can be assumed that the actual occurrence of affected babies by thalidomide continues being as frequent as denounced ten years ago.

Thalidomide analogues as anticancer drugs.

Preclinical and clinical data relating to these thalidomide analogues, as well as ENMD-0995, are reviewed herein and the patents and preclinical findings for these agents are discussed.

The evolution of thalidomide and its IMiD derivatives as anticancer agents

A series of immunomodulatory drugs — created by chemical modification of thalidomide — have been developed to overcome the original devastating side effects, and their powerful anticancer properties mean that these drugs are now emerging from thalidmide's shadow as useful anticancer agents.

Thalidomide inhibits angiogenesis in embryoid bodies by the generation of hydroxyl radicals.