BMP-Mimetics - A test system to identify bone morphogenic protein (BMP)-mimetics
Keywords: Stammzelle, Differenzierung, induzierte pluripotente Stammzelle, mesenchymal, osteogen, stem cell, differentiation, induced pluripotent stem cell, mesenchymal, bone morphogenic proteins
In this context, a phenotypic assay in murine embryonic stem cells, designed to combine assets of a high-throughput format with physiological (morphogenetic) relevance was developed to identify BMP-mimetics. A chemical biology approach employing known cardiogenic compounds enabled the characterization of BMP signaling selectivity compared to other develop-mental pathways for the first time in this assay system. Mechanistic as well as technical assay parameters were optimized and allowed pilot-screening of a 1,408 compounds-comprising library. Ten small molecule BMP mimetics were identified and validated via IC50 determination and a set of orthogonal assays. Their utility as chemical tools for stem cell technologies and as regenerative therapeutics will have to be explored in future studies.
- Unique, innovative, stem cell-based assay for the identification of BMP-mimetic agents
- Ligand-independent BMP-mimetic compounds with novel mode-of-action
The test system as well as novel BMP-mimetic compounds are offered for licensing and further biotechnological and/or therapeutic development.
Ready-to-screen assay format for up to 50,000 compounds comprising libraries. In addition, several functionally validated BMP mimetic compounds have been identified, including first profiling of structure.
Feng, L., et al. (2016) Discovery of a small-molecule BMP sensitizer for human embryonic stem cell differentiation. Cell Reports 15: 2063-75.
Ali, I.H. & Brazil, D.P. (2014) Bone morphogenetic proteins and their antagonists: current and emerging clinical uses. British Journal of Pharmacology 171: 3620-32.
Eine Erfindung der TU Dortmund.