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Accession IconGSE95248

Ventromorphins: A new class of small molecule activators of the canonical BMP signaling pathway

Organism Icon Mus musculus
Sample Icon 20 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

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Here we describe three new small-molecule activators of BMP signaling found by high throughput screening of a library of ~600,000 small molecules. Using a cell-based luciferase assay in the BMP4-responsive human cervical carcinoma clonal cell line, C33A-2D2, we identified three compounds with similar chemotypes, each ventralized zebrafish embryos and stimulated increased expression of the Bmp target genes, bmp2b and szl. Because these compounds ventralize zebrafish embryos, we have termed them ventromorphins. As expected for a BMP pathway activator, they induce the differentiation of C2C12 myoblasts to osteoblasts. Affymetrix RNA analysis confirmed the differentiation results and showed that ventromorphin treatments elicits a genetic response similar to BMP-4 treatment. Unlike isoliquiritigenin (SJ000286273), a flavone that maximally activates the pathway after 24 hours of treatment, all three ventromorphins induced SMAD1/5/8 phosphorylation within 30 minutes of treatment and achieved peak activity at 30 minutes or 1 hour, indicating that their direct responses are consistent with activated BMP signaling.
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