Hypothesis: thalidomide embryopathy-proposed mechanism of action.

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Stephens TD, Fillmore BJ

Hypothesis: thalidomide embryopathy-proposed mechanism of action.

Teratology. 2000 Mar;61(3):189-95.

PubMed ID

10661908 [ View in PubMed

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Abstract

We propose that thalidomide affects the following pathway during limb development: Growth factors (FGF-2 and IGF-I) attach to receptors on limb bud mesenchymal cells and initiate some second messenger system (perhaps SP-1), which activates alphav and beta3 integrin subunit genes. The resulting alphav beta3 integrin proteins stimulate angiogenesis in the developing limb bud. Several steps in this pathway depend on the activation of genes with primarily GC promoters (GGGCGG). Thalidomide, or a hydrolysis or metabolic breakdown product, specifically binds to GC promoter sites and inhibits the transcription of those genes. Inhibition of the genes interferes with normal angiogenesis, which results in truncation of the limb.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Thalidomide	DNA	Nucleotide	Humans	Yes	Intercalation	Details