SJ000291942

Description: SJ000291942 is a new small-molecule activator of the canonical BMP (bone morphogenetic proteins) signaling pathway. BMPs are members of the transforming growth factor beta (TGFbeta) family of secreted signaling molecules. SJ000291942 was 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, SJ000291942 can ventralize zebrafish embryos and stimulate increased expression of the BMP target genes, bmp2b and szl. Because SJ000291942 ventralizes zebrafish embryos, it was termed as 'ventromorphins.' As expected for a BMP pathway activator, SJ000291942 induces the differentiation of C2C12 myoblasts to osteoblasts. Affymetrix RNA analysis confirmed the differentiation results and showed that SJ000291942 treatment elicits a genetic response similar to BMP4 treatment. Unlike isoliquiritigenin (SJ000286237), a flavone that maximally activates the pathway after 24 h of treatment, SJ000291942 induced SMAD1/5/8 phosphorylation within 30 min of treatment and achieved peak activity within 1 h, indicating that their responses are consistent with directly activating BMP signaling.

References: ACS Chem Biol. 2017 Sep 15; 12(9):2436-2447.