PHD Student

KEY WORDS: drug design, anticancer drugs, enzyme inhibitors, macromolecular structure

Principal Investigator: dr hab. Milosz Ruszkowski

Research topic: drug discovery

I. Project description

Cancer cells reprogram their proline metabolism to enable survival, proliferation and metastatic spread. In the final reaction of proline biosynthesis, δ1-pyrroline-5-carboxylate (P5C) reductase converts P5C into proline utilizing NAD(P)H as a cofactor. The aim of this project is to develop inhibitors of PYCR1, a human P5C reductase, which has emerged as a novel intervention point to deregulate the metabolism of malignant cells. To this end, we will combine high-throughput screening with rationalized drug design and use both wet-lab experiments and computer-aided methods. First, we will identify the so-called hit compounds, able to slow down PYCR1 activity to some extent. Then, we will optimize these molecules to produce more potent inhibitors. The optimization steps will be guided by 3D structures of these molecules binding to PYCR1, which will suggest changes to be made for improved efficacy. New compounds will be synthesized and their potency against PYCR1 activity will be tested in vitro and in cellulo.

IBCH PAS is one of leading research institutes in Poland and conducts research in the field of chemistry, molecular biology and biomedicine. The Institute provides access to cutting-edge research equipment.

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