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

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Angebotsbeschreibung

Ref.-Nr. 5063

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). 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.

Keywords: Stammzelle, Differenzierung, induzierte pluripotente Stammzelle, mesenchymal, osteogen, stem cell, differentiation, induced pluripotent stem cell, mesenchymal, bone morphogenic proteins

Commercial Opportunities

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

Competitive Advantages

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

Current Status

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. A European priority application is pending.

Relevant Publications

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.


bitte Kontaktieren Sie mich zu diesem angebot.

Prof. Dr. Frank Entschladen
+49.208-94105-20
fe@provendis.info

Prof. Dr. Frank Entschladen

Dieses Angebot

Kontakt

PROvendis GmbH · Schloßstr. 11 – 15
D – 45468 Mülheim an der Ruhr
T +49 (0)208 94105-0 · kontakt@provendis.info