Identification of optimized Aurora Kinase A PROTACs with suitable PK properties for in vivo proof-of-concept studies (OPTIMAPK).

15 July 2023 → 14 October 2024
Regional and community funding: Industrial Research Fund
Research disciplines
  • Medical and health sciences
    • Drug discovery and development not elsewhere classified
    • Pharmacokinetics
Pharmacokinetics PK modelling Aurora kinase A PROTACs
Project description

Proteolysis targeting chimeras (PROTACs) are small molecule drugs able to selectively remove a disease-causing protein from cells and have emerged as a game-changing technology in drug discovery. We used this technology to induce the removal of Aurora Kinase A, a protein with crucial tumour growth-inducing functions in cancers such as leukemia, prostate cancer and neuroblastoma. We were able to identify a state-of-the-art PROTAC with very promising anti-tumour activity. This inspired us to start an optimization campaign, which led to new series of AURKA PROTACs with even improved anti-tumour effects.

In this project we will study their metabolism and pharmacokinetic (DMPK) characteristics in vitro as to move to a mouse study. These results, together with physiological based pharmacokinetic (PBPK) computer modelling, will be instrumental in the selection of a suitable lead candidate to further elaborate the therapeutic potential in a mouse model.