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- W4210677642 abstract "We report on the feasibility to harness embryonic development in vitro for the identification of small-molecule cytokine mimetics and signaling activators. Here, a phenotypic, target-agnostic, high-throughput assay is presented that probes bone morphogenetic protein (BMP) signaling during mesodermal patterning of embryonic stem cells. The temporal discrimination of BMP- and transforming growth factor-β (TGFβ)-driven stages of cardiomyogenesis underpins a selective, authentic orchestration of BMP cues that can be recapitulated for the discovery of BMP activator chemotypes. Proof of concept is shown from a chemical screen of 7000 compounds, provides a robust hit validation workflow, and afforded 2,3-disubstituted 4H-chromen-4-ones as potent BMP potentiators with osteogenic efficacy. Mechanistic studies suggest that Chromenone 1 enhances canonical BMP outputs at the expense of TGFβ-Smads in an unprecedented manner. Pharmacophoric features were defined, providing a set of novel chemical probes for various applications in (stem) cell biology, regenerative medicine, and basic research on the BMP pathway." @default.
- W4210677642 created "2022-02-08" @default.
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- W4210677642 date "2022-02-02" @default.
- W4210677642 modified "2023-09-25" @default.
- W4210677642 title "Probing Embryonic Development Enables the Discovery of Unique Small-Molecule Bone Morphogenetic Protein Potentiators" @default.
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- W4210677642 doi "https://doi.org/10.1021/acs.jmedchem.1c01800" @default.
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