Centro Therapeutics
Degrading Centrosome Clustering Proteins
Centro Therapeutics is an entrepreneurial team created by researchers from Lancaster University. We work on developing new small molecule degraders to target proteins involved in centrosome clustering, considered an Achilles’ heel of hard-to-treat cancer.
First-in-class small-molecule PROTAC targeting centrosome clustering protein.
The Problem
Difficult-to-treat cancers such as Triple-negative breast cancer, Brain tumours, Pancreatic cancer and Metastatic disease display decreased overall survival and lack long-term effective treatments. These tumours have a common feature: an increased number of centrosomes.
Healthy cells have only two centrosomes which allow correct cell division. However, cancer cells with centrosome amplification need accessory proteins to help cell division by clustering extra centrosomes. The requirement for centrosome clustering proteins in cancer but not normal cells creates a therapeutically targetable Achilles’ heel.
Our Solution
PROTAC's - New Class of Drugs
PROTACs (proteolysis targeting chimaeras) are a new class of drugs that use the cell’s machinery to destroy target proteins by marking them as unwanted, prompting their degradation.
How PROTACs work
Our PROTAC is a small molecule with two binding regions: at one end it binds to a centrosome clustering protein. At the other end is a region that binds to an E3 ubiquitin ligase, part of the natural disposal cellular machinery. The regions are joined via a linker which is important for PROTAC specificity and function. Inside the cells, a PROTAC forms a complex with the target protein and ubiquitin ligase. This complex will mark the protein to be recognised and destroyed by the disposal system.
Developing PROTACs to degrade centrosome clustering proteins is a powerful approach to target centrosome amplification. We have successfully developed small-molecule degraders for a protein required for centrosome clustering, a clinically relevant alternative to siRNA-induced protein knockdown and small-molecule inhibitors.
Lead Degrader
Our first-in-class lead degrader displays strong inhibitory growth effects in triple-negative breast cancer cells with centrosome amplification and shows considerably increased potency against and selectivity for cancer cells compared to inhibitor molecules against the same target. Therefore, our degrader should be considered a new tool, both for studying the centrosome clustering mechanism and importantly, further investigated as a new therapeutic avenue for a wide range of cancers.
We aim to explore the potential markets for research and clinical use of the novel PROTAC and determine the next steps required to develop the small molecule before launching the product to market.
Benefits
Cancer-specific mechanism targeting centrosome amplification
Applicable to a broader spectrum of hard-to-treat cancer types
Greater efficacy than target inhibitor (73-fold more potent)
Improved safety: Low dosage administration
Potential oral administration
Relevant as a research tool to study target degradation
Meet the Team
Morgan Gadd
(Co-Investigator)
Collaborate with us!
info@centrotherapeutics.com