Researchers at St. Jude discovered three new structurally similar small-molecule activators of Bone Morphogenetic Proteins (BMPs) signaling. Treatment with these compounds elicits a genetic response similar to BMP4, which induces differentiation of cerebellar granule neuronal progenitors and tumor cells from a subgroup of medulloblastoma. BMPs are expensive to produce and do not cross the blood-brain barrier, making them poor clinical candidates. These activator compounds are cheaper to make and more deliverable to the brain than BMP molecules. Thus, they are excellent candidates for treating diseases caused by defective or diminished BMP signaling, including medulloblastoma, juvenile polyposis syndrome, hereditary pulmonary arterial hypertension, obesity osteoporosis and kidney disease. They may also be used for cartilage repair or bone formation.
Bone Morphogenetic Proteins (BMPs), cell -based assay, BMP4, cervical carcinoma, medulloblastoma
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Related Scientific References
Genthe JR, Min J, Farmer DM, Shelat AA, Grenet JA, Lin W, Finkelstein D, Vrijens K, Chen T, Guy RK, Clements WK, Roussel MF. ACS Chem Biol. 2017 Sep 15;12(9):2436-2447. doi: 10.1021/acschembio.7b00527. Epub 2017 Aug 29. PMID: 28787124
Zhao, Roussel et al., “Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development,” Genes & Dev., 2008, doi: 10.1101/gad.1636408
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