Background

Bicyclic peptides are small polypeptides that exhibit properties typical of both monoclonal antibodies (high target specificity and affinity) and small molecules (high stability and good tissue penetration).

The present invention reports the discovery of bicyclic peptides that inhibit urokinase-type plasminogen activator (huPA) with low nanomolar affinity and are significantly more specific than the late clinical stage small molecule inhibitor Upamostat (WX-671, Mesupron). huPA plays critical roles in the processes of cancer proliferation and metastases and it has also been related to the pathology of rheumatoid arthritis.

Technology Overview

The present invention describes the discovery of bicyclic peptide derivatives obtained by conjugating linear peptide sequences to a trifunctional small organic molecule (1,3,5-tris(bromomethyl)-benzene). Specifically, it refers to two peptide ring compounds (and their synthesis) comprising a benzene core connected via three covalent bonds to three cysteine residues present in the peptide sequence. In vitro studies showed that the herein described bicyclic peptides inhibited huPA with Kis ranging from 4.27 and 31.4 nM; thus, making these compounds efficient active ingredients in the treatment of pathological conditions (e.g., breast cancer, pancreatic cancer and rheumatoid arthritis) in which huPA has been showed to play a key role.

For the proposed therapeutic uses, these peptides showed low toxicity, tunable half-life and can be formulated in pharmaceutical compositions for parenteral administration.

Benefits

High binding affinity
Exquisite target specificity
Good tissue penetration
High plasma stability
Tunable half-life

Applications

Cancer treatment

Rheumatoid arthritis treatment

Opportunity

Open to collaborative projects to further develop the technology and/or licensing.

Bicyclic Peptide Inhibitors of the Human Urokinase-Type Plasminogen Activator (HUPA)

Patents

IP Status

Seeking