Modern drugs are molecules that interfere with the activity of a specific protein related to a target disease. Within this realm, new molecules capable of interfering with protein-protein interactions (PPIs) are in the heart of modern drug discovery. However, the discovery or de-novo design of new molecules is often hampered by the lack of structural information of the PPI interfaces and suitable experimental binding techniques. This often prompted the conclusion that PPIs are “undruggable” targets. By fostering a multidisciplinary collaboration, we are able to identify new peptides and small molecules capable of interfering with PPIs. These are high affinity & specificity protein-protein interaction modulators.
This invention relates to the inhibition of the HIF prolyl hydroxylase (PHD protein). PHD tags (via hydroxylation) HIF, advancing its degradation. Therefore, modulators preventing PHD/HIF interaction can stabilize HIF, enhancing its cellular activity. Drugs such as Daprodustat blocks PHD catalytic activity and is a clinically-approved drug.

Using our propriety algorithms and methods, we identified peptides capable of interfering with HIF-PHD interaction. These pave the way for the development of new therapeutics with an improved safety profile as well as for the discovery of small molecule protein-protein interaction inhibitors of PHD/HIF.

UNMET NEED
The development of safe and specific HIF-Prolyl Hydroxylase Domain (PHDs) inhibitors for –
• Cancer
• Anemia
• Bone/skin regeneration
• HIF related diseases

OUR SOLUTION
Peptides interfering with PHD/HIF interactions

APPLICATIONS
• Cancer
• Anemia
• Bone/skin regeneration
• HIF related diseases

STATUS
New potent peptides have been identified in in vitro screen for PHD/HIF blocking activity.

INTELLECTUAL PROPERTY
The structural features of the peptides are confidential

REFERENCES
1. https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1010874