ArticleProceedings of the National Academy of Sciences of the United States of America2009
Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 253 citations in OpenAlex.
- Genetic Susceptibility to Drug Teratogenicity: A Systematic Literature Review.Frontiers in genetics · 2021Pooled it
- Multiple congenital malformations in a burrowing owl (Athene cunicularia) from Southern Brazil.Veterinary research communications · 2026Article
- Thalidomide as an Adjunctive Therapy for HIV-Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome: A Case Series.Open forum infectious diseases · 2025Article
- Monoterpenoid fluorophthalimide IMiDs that lack human cereblon binding: synthesis and anti-proliferative, anti-angiogenic and anti-inflammatory activities.Biochemical and biophysical research communications · 2025Article
- New insight into teratogenic effects of (S)-thalidomide in zebrafish embryos growing inside the chorion and subjected to electric pulses.Scientific reports · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Deep tissue sensing of chiral molecules using polarization-enhanced photoacoustics.Science advances · 2025Article
- Embryoid Body Test: A Simple and Reliable Alternative Developmental Toxicity Test.International journal of molecular sciences · 2024Review
- RosetteArraybioRxiv : the preprint server for biology · 2024Article
- Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma.Biomolecules · 2024Article
- Molecular signatures of angiogenesis inhibitors: a single-embryo untargeted metabolomics approach in zebrafish.Archives of toxicology · 2024Article
- Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity.Archives of toxicology · 2024Article
- Proteolysis-targeting chimeras with reduced off-targets.Nature chemistry · 2024Article
- Sex-based impact of pancreatic islet stressors in GluCreERT2/Rosa26-eYFP mice.The Journal of endocrinology · 2023Article
- Thalidomide upper limb embryopathy - pathogenesis, past and present management and future considerations.The Journal of hand surgery, European volume · 2023Review
- A New Strategy for the Old Challenge of Thalidomide: Systems Biology Prioritization of Potential Immunomodulatory Drug (IMiD)-Targeted Transcription Factors.International journal of molecular sciences · 2023Article
- Maternal Cigarette Smoking and Congenital Upper and Lower Limb Differences: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2023Review
- Cohesin: an emerging master regulator at the heart of cardiac development.Molecular biology of the cell · 2023Article
- Novel, thalidomide-like, non-cereblon binding drug tetrafluorobornylphthalimide mitigates inflammation and brain injury.Journal of biomedical science · 2023Article
- Augmentation of Pectoral Fin Teratogenicity by Thalidomide in Human Cytochrome P450 3A-Expressing Zebrafish.Pharmaceuticals (Basel, Switzerland) · 2023Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Thalidomide is a potent teratogen that induces a range of birth defects, most commonly of the developing limbs. The mechanisms underpinning the teratogenic effects of thalidomide are unclear. Here we demonstrate that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and provide an explanation for its action at the cell biological level. Antiangiogenic but not antiinflammatory metabolites/analogues of thalidomide induce chick limb defects. Both in vitro and in vivo, outgrowth and remodeling of more mature blood vessels is blocked temporarily, whereas newly formed, rapidly developing, angiogenic vessels are lost. Such vessel loss occurs upstream of changes in limb morphogenesis and gene expression and, depending on the timing of drug application, results in either embryonic death or developmental defects. These results explain both the timing and relative tissue specificity of thalidomide embryopathy and have significant implications for its use as a therapeutic agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.