ArticleScientific reports2020
Thalidomide Inhibits Human iPSC Mesendoderm Differentiation by Modulating CRBN-dependent Degradation of SALL4.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Engineered tissues and strategies to overcome challenges in drug development.Advanced drug delivery reviews · 2020Pooled it
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Drug Repurposing in Veterinary Oncology: Myth or Reality?Veterinary sciences · 2025Review
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Review
- Comparison of the efficacy of thalidomide combined with low-dose rituximab and low-dose rituximab alone in the treatment of steroid-resistant/refractory adult patients with primary immune thrombocytopenia: an open-label trial.Frontiers in medicine · 2025Article
- Profiling assay performance in the DevTox germ layer reporter platform.Current research in toxicology · 2025Article
- Article
- In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between.Biomedicines · 2024Review
- Discovery of KT-474─a Potent, Selective, and Orally Bioavailable IRAK4 Degrader for the Treatment of Autoimmune Diseases.Journal of medicinal chemistry · 2024Article
- Identification of SALL4 Expressing Islet-1+ Cardiovascular Progenitor Cell Clones.International journal of molecular sciences · 2023Article
- The DevTox Germ Layer Reporter Platform: An Assay Adaptation of the Human Pluripotent Stem Cell Test.Toxics · 2022Article
- Optimization of the TeraTox Assay for Preclinical Teratogenicity Assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- PROTACs: past, present and future.Chemical Society reviews · 2022Review
- AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss.European journal of medicinal chemistry · 2021Article
- PLZF and its fusion proteins are pomalidomide-dependent CRBN neosubstrates.Communications biology · 2021Article
- In vitro teratogenicity testing using a 3D, embryo-like gastruloid system.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- An Evaluation of Human Induced Pluripotent Stem Cells to Test for Cardiac Developmental Toxicity.International journal of molecular sciences · 2021Article
- Thalidomide affects limb formation and multiple myeloma related genes in human induced pluripotent stem cells and their mesoderm differentiation.Biochemistry and biophysics reports · 2021Article
- Engineering spatial-organized cardiac organoids for developmental toxicity testing.Stem cell reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure to thalidomide during a critical window of development results in limb defects in humans and non-human primates while mice and rats are refractory to these effects. Thalidomide-induced teratogenicity is dependent on its binding to cereblon (CRBN), the substrate receptor of the Cul4A-DDB1-CRBN-RBX1 E3 ubiquitin ligase complex. Thalidomide binding to CRBN elicits subsequent ubiquitination and proteasomal degradation of CRBN neosubstrates including SALL4, a transcription factor of which polymorphisms phenocopy thalidomide-induced limb defects in humans. Herein, thalidomide-induced degradation of SALL4 was examined in human induced pluripotent stem cells (hiPSCs) that were differentiated either to lateral plate mesoderm (LPM)-like cells, the developmental ontology of the limb bud, or definitive endoderm. Thalidomide and its immunomodulatory drug (IMiD) analogs, lenalidomide, and pomalidomide, dose-dependently inhibited hiPSC mesendoderm differentiation. Thalidomide- and IMiD-induced SALL4 degradation can be abrogated by CRBN V388I mutation or SALL4 G416A mutation in hiPSCs. Genetically modified hiPSCs expressing CRBN E377V/V388I mutant or SALL4 G416A mutant were insensitive to the inhibitory effects of thalidomide, lenalidomide, and pomalidomide on LPM differentiation while retaining sensitivity to another known limb teratogen, all-trans retinoic acid (atRA). Finally, disruption of LPM differentiation by atRA or thalidomide perturbed subsequent chondrogenic differentiation in vitro. The data here show that thalidomide, lenalidomide, and pomalidomide affect stem cell mesendoderm differentiation through CRBN-mediated degradation of SALL4 and highlight the utility of the LPM differentiation model for studying the teratogenicity of new CRBN modulating agents.
Indexed as
Identifiers
What OpenQuestion holds
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.