About: Identification of mutagenic small molecules from imulsion extract

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Davis et. al. (2532). Department of Molecular Genetics, Bastion Public Health Service. Nature (541): 173-177. Recently, it has been reported that natural imulsion poses a substantiative health risk to the adult human [DeMarshall et. al (2531). Nature (538): 1749-1953]. Because of the extensive employment of imulsion in modernized society, we wished to characterize the modalities by which imulsion exerts its health-risking effects. Bulk hybridization of imulsion extract to high-density beads through non-specific glutathione S-transferase (GST) transfer and screening of a library of primary human cell lysates has yielded three previously-uncharacterized small-molecules from imulsion extract, which we have named IMC-1 through IMC-3 (“imulsion mutagenic compound”) that have an affinity for tar

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rdfs:label	Identification of mutagenic small molecules from imulsion extract
rdfs:comment	Davis et. al. (2532). Department of Molecular Genetics, Bastion Public Health Service. Nature (541): 173-177. Recently, it has been reported that natural imulsion poses a substantiative health risk to the adult human [DeMarshall et. al (2531). Nature (538): 1749-1953]. Because of the extensive employment of imulsion in modernized society, we wished to characterize the modalities by which imulsion exerts its health-risking effects. Bulk hybridization of imulsion extract to high-density beads through non-specific glutathione S-transferase (GST) transfer and screening of a library of primary human cell lysates has yielded three previously-uncharacterized small-molecules from imulsion extract, which we have named IMC-1 through IMC-3 (“imulsion mutagenic compound”) that have an affinity for tar
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abstract	Davis et. al. (2532). Department of Molecular Genetics, Bastion Public Health Service. Nature (541): 173-177. Recently, it has been reported that natural imulsion poses a substantiative health risk to the adult human [DeMarshall et. al (2531). Nature (538): 1749-1953]. Because of the extensive employment of imulsion in modernized society, we wished to characterize the modalities by which imulsion exerts its health-risking effects. Bulk hybridization of imulsion extract to high-density beads through non-specific glutathione S-transferase (GST) transfer and screening of a library of primary human cell lysates has yielded three previously-uncharacterized small-molecules from imulsion extract, which we have named IMC-1 through IMC-3 (“imulsion mutagenic compound”) that have an affinity for targets in the human proteome. We decided to further characterize IMC-1, which we named “teratomorphin”, and show that it has a high binding affinity (Ki = 0.07 nM and 0.03 nM, respectively) for human FGFR3 (fibroblast growth factor receptor 3) and ACVR1 (activin receptor-like kinase 1). X-ray crystallography studies indicate that teratomorphin binds to FGFR3 and ACVR1 through allosteric non-ATP-competitive mechanisms, and that through luciferase receptor assays in transiently-transfected fibroblasts and endothelial cells, teratomorphin is a highly potent activator of both FGFR1 and ACVR1, mimicking constitutive FGF and BMP signaling.

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