Prof. Chaim Gilon, The Hebrew University of Jerusalem
Prof. Prof. Rachel Bar-Shavit, Hadassah Medical Center

Application

  • Peptidomimetics have gained significant interest in drug development due to their potential advantages over peptides. While peptides can be effective in targeting specific biological processes, they often suffer from limitations such as poor stability, susceptibility to enzymatic degradation, and limited cell penetration. Peptidomimetics address these challenges by incorporating non-peptide components that improve stability, bioavailability, and pharmacokinetic properties.
  • Target-specific approaches are recognized as the basis for novel cancer therapeutics. Protease-Activated-Receptors (PARs), a G Protein-Coupled Receptor (GPCR), play central roles in tumor progression. PARs are over-expressed in a wide range of epithelial malignancies relative to the normal epithelium, thus offering the opportunity for a tumor-specific drug.
  • The PAR C-terminal PH-binding domain binds to other proteins that have a key role in tumorigenesis and comprise a PH-domain, suggesting that this domain might be effectively targeted by a novel therapeutic.

Our Innovation

We develop and characterize a “lead cyclic peptidomimetic” compound of PAR4-PH binding domain for available cancer drug.

Advantages

  • Use of backbone cyclization procedure that enables the development of cyclic peptides leaving intact residues that are part of the natural linear peptide, which may be essential for the peptide’s biological activity, particularly if the peptide is short.
  • Use of the PH domain of PAR4 as a target due to its unique properties: potent stem cell that plays a robust function in the induction of beta-catenin stabilization and beta-catenin transcriptional activity.

Opportunity

The opportunity for developing an efficient drug that will potently inhibit breast cancer stem cells and is expected also to inhibit a wide range of tumors (will be tested at a later stage), is of high therapeutic value.  Drug-developing companies for therapeutic medicaments can be interested in such a novel target.