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Kurzfassung

A test system to identify bone morphogenic protein (BMP)-mimetics

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Hintergrund

Small molecule activators of the Bone Morphogenetic Protein (BMP)-signaling pathway hold promise for many applications in stem cell research such as (cost-)efficient and robust mesodermal differentiation from pluripotent stem cells (e.g., ESCs, iPSCs) or as therapeutics for degenerative bone (and cartilage) diseases (please see relevant publications).

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Lösung

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.  

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-activity relationships by means of medicinal chemistry.

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Vorteile

• Unique, innovative, stem cell-based assay for the identification of BMP-mimetic agents
• Ligand-independent BMP-mimetic compounds with novel mode-of-action

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Service

The test system as well as novel BMP-mimetic compounds are offered for licensing and further biotechnological and/or therapeutic development.