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Notch-inhibitor for cancer treatment

Innovative inhibitors of Notch trafficking and signalling for the treatment of cancer

Ansprechpartner

Dr. Sabina Heim

Kurzbeschreibung

Challenge

The Notch signaling pathway plays a key role in development and cell-fate determination and its aberrant activity leads to developmental disorders and cancer. So far therapeutic interventions of aberrant Notch signaling, for example in cases of T cell-lineage acute lymphoblastic leukemia (T-ALL) at present are aimed at the level of ligand-binding and gamma-secretase cleavage. Several inhibitors of the gamma-secretase (GSI) were tested for their anti-cancer activity but failed due to significant side effects. Therefore novel strategies would be highly desired. Hence trafficking and regulation of Notch signalling could provide potential new therapeutic targets.
 
Technology
The invention relates to five novel compounds (FLI-6, FLI-14, FLI-15, FLI-19, FLI-20)  as potential inhibitors of the notch signalling pathway for the treatment of cancer. These compounds address different steps in trafficking and regulation of Notch signalling. FLI-6 acts on a very early step in recruitment of cargo to endoplasmic reticulum exit sites and therefore affects the general transport through the secretory pathway. FLI-15 and -20 are novel direct GSIs whereas FLI-14 and -19 inhibit Notch and amyloid precursor protein (APP) processing in cells. Therefore these compounds can be promising starting points for the development of innovative anti-cancer therapeutics.
Further Reading
Krämer et al. – Nature Chem Biol. 2013 Sep 29; 9:731-8.

Technologie

Entwicklungsstand

European patent application filed in June 2012. All compounds were validated in in vitro and cellular assays using C2C12 cells as well as in vivo in a well-established zebrafish model.

Vorteile/Nutzen

The invention relates to five novel compounds as potential inhibitors of the notch signalling pathway for the treatment of cancer. These compounds can be promising starting points for the development of innovative anti-cancer therapeutics.

Publikationsnummer

WO 2013/178821

Ansprechpartner Patentverwertung

Dr. Sabina Heim
Technology Manager
Ascenion GmbH

T: +49 (0)531 618120-91
F: +49 (0)531 618120-98
heim@ascenion.de

Angebot ist interessant für

Commercial Opportunity: The technology is offered for co-development or in-licensing.

 

Anschrift

  • Beutenbergstraße 11
  • 07745 Jena

Ansprechpartner

 
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