Our collaborative projects involve designing and synthesizing novel small molecule compounds targeting various diseases. Our research areas include antimicrobials, receptor modulators, anticancer compounds, and more, with a focus on sustainable synthetic methods.
Covalent Warheads to Tackle Drug-Resistant Tuberculosis

Covalent warheads are functional groups or chemical moieties within a molecule that tend to form a covalent bond with nucleophilic residues commonly found in protein active sites, such as cysteine, serine, or lysine residues. Once the covalent bond is formed between the compound containing the covalent warhead and the target, inhibition continues until the target protein undergoes degradation or turnover. This prolonged duration of action can lead to enhanced potency with lower doses of the drug to achieve long-lasting pharmacological effects, reduced risk of off-target effects, and improved safety profiles. This project aims to explore the potential of our recently identified covalent warheads containing compounds to address the issue of drug-resistant tuberculosis.

For further information, please contact Jayendra Patel.

Drug Repurposing to Discover Novel Antibacterials

The project aims to repurpose G-protein coupled-receptor (GPCR) ligands, existing drugs or clinical candidates, as potential antibiotics to target multi-drug resistant bacteria. This approach leverages known drug characteristics, reducing development time and cost while increasing the likelihood of regulatory approval. Targeting GPCRs offers a novel strategy to address the urgent need for new antibacterial agents. For example, recently we have repurposed etrasimod (Zore et al. 2022) as antibacterial agent against Gram-positive bacteria. Besides this, we are interested in drug optimization to improve potency and to prevent problematic issues, such as toxicity (Zore et al. 2021; Zore et al. 2024).

For further information, please contact Jayendra Patel.

Marine Bioactive Compounds

Marine sponges and other marine organisms are a rich source of novel compounds with unique structural features and drug-like properties. We aim to synthesize bioactive marine compounds and design their simplified analogs. Marine compounds are considered as an extremely valuable source for drug scaffolds for many different biological targets e.g. cancer, ion channels, bacteria and parasites. This project is a continuum of EU-FP7 MAREX (Exploring Marine Resources for Bioactive Compounds: From Discovery to Sustainable Production and Industrial Applications) that was coordinated by the Faculty of Pharmacy. Currently we have an antileishmanial bisindole project with the University of Urbino.

For further information, please contact Paula Kiuru.

Membrane-Bound Pyrophosphatase Inhibitors

Membrane-bound pyrophosphatase inhibitors (mPPases) offer a different approach for further development of novel drugs against e.g., malaria (Plasmodium spp.). These mPPase enzymes hydrolyze pyrophosphate, a by-product of many biological processes. Besides taking care of excess pyrophosphate, the energy released through hydrolysis of phosphoanhydride bonds is coupled with the pumping of protons or sodium ions thus creating an ion gradient across the membrane. Consequently, mPPases play an important role in the survival of many organisms under diverse stress situations due to osmotic stress or other energy limitations. By developing nonphosphorus inhibitors targeting mPPase, our intention is to block the essential ion pump of these parasites as a different approach for further development of novel drugs against also other diseases caused by pathogenic protozoan parasites. In collaboration with the groups of Prof. Adrian Goldman (UH & University of Leeds), Prof. Seppo Meri (UH), and Doc. Henri Xhaard (UH).

For further information, please contact Niklas Johansson.

Metallo-β-lactamase Inhibitors

Bacterial pathogens are often not eradicated by antibiotic treatment due to the production of zinc-containing metallo-β-lactamases (MBL) which directly catalyze decomposition of β-lactam antibiotics. MBL inhibitors are planned to use on combination with β-lactam antibiotics. We are designing and synthesizing novel MBL inhibitors in collaboration with Prof. Chris Schofield (University of Oxford) and Prof. Päivi Tammela (UH) targeting ESKAPE pathogens, such as K. pneumoniae, E. coli and P. aeruginosa.

For further information, please contact Paula Kiuru (PI) or Manuela Voráčová.

Modulators of Protein-Protein Interaction of PREP

Prolyl oligopeptidase (PREP) is a proteolytic enzyme, but it also regulates many important processes in the human body via direct interactions with other proteins such as α-synuclein (αSyn), Tau, and protein phosphatase 2A (PP2A). These interactions result in increased αSyn and Tau aggregation, decreased PP2A activity and autophagy, and increased reactive oxygen species (ROS) production.  A novel PREP ligand series comprising non-peptidic compounds which display only a weak inhibitory activity are among the most potent modulators of the protein-protein interaction mediated functions. These new PREP ligands have also been used to identify a new binding site on PREP, which is more important for modulation of the protein-protein interaction mediated functions than the active site. This project has resulted in Polku Therapeutics Ltd, a spin out from University of Helsinki. Collaborators: Timo Myöhänen, Faculty of Medicine, University of Helsinki, and Maija Lahtela-Kakkonen, School of Pharmacy, University of Eastern Finland.

For further information, please contact Erik Wallén or Henri Pätsi.


Optimizing Synthesis of Pharmaceuticals by Machine Learning

In every drug discovery campaign, the synthesis of novel molecules is the most resource-intense stage. The recent advances in artificial intelligence (AI) and machine learning (ML) have also been utilized to develop data-driven tools for reaction planning in organic synthesis. In our project, we aim to develop AI models for reaction condition selection and reaction planning using language models, deep neural networks, and other deep learning techniques. The project consists of classical experimental laboratory syntheses, quantitative analytical chemistry, and programming with Python programming language. The project has collaborators both in academia and industry. The project has been funded by Finnish Research Impact Foundation (2022-2024).

For further information, please contact Juri Timonen.

Protein Kinase Modulators

Protein kinases represent promising targets for treating a range of diseases, including autoimmune disorders, cardiovascular diseases, cancer, and inflammatory disorders. Our research group has had a long-lasting interest in kinase modulators. Currently our primary emphasis is on protein kinase C (PKC) and protein kinase B (PKB or AKT), while also considering other kinases such as protein kinase A (PKA). 

PKB and PKC serve as significant regulators of cell proliferation, survival, and growth. PKB activation has been demonstrated to possess both protective and reparative effects on tissue damage in normally non-proliferating cell types, such as cardiomyocytes. In addition, several studies demonstrated that activation of PKC could be a promising strategy for treatment of cancer, Alzheimer’s disease, and cardiac fibrosis. Our aim is to design and synthesize new small molecule compounds with potential to enhance the regenerative capacity of the heart after e.g., infarction or to inhibit cardiac remodeling, to selectively affect cancer cells, and to prevent/reduce neuronal damage.

For further information, please contact Riccardo Provenzani and Katia Sirna (PKC, PKA), or Tanja Bruun (PKB).

Protein-Protein Interaction Inhibitors for MID1

Protein phosphatase 2A (PP2A) is the most important phosphatase in the body and it has been linked also to neurodegenerative diseases. The activity of PP2A can be regulated through the Midline 1 (MID1) protein, as there is a protein-protein interaction between MID1 and the catalytic subunit of PP2A, where also a third protein called α4 is participating. We have found a binding site on MID1 for small molecules which disrupt the binding of α4 to MID1 and thereby also the formation of the tripartite complex of the proteins. The new compounds we are currently developing inhibit the protein-protein interaction between MID1 and α4, resulting in an activation of PP2A. Collaborators: Timo Myöhänen, Faculty of Medicine, University of Helsinki, and Maija Lahtela-Kakkonen, School of Pharmacy, University of Eastern Finland.

For further information, please contact Erik Wallén or Henri Pätsi.



Springboard for excellence in advanced development of antibacterials

European Union’s Horizon 2020 Twinning project for building an excellence platform in the area of advanced discovery of novel antibacterial drugs to strengthen the research potential of the Latvian Institute of Organic Synthesis. We are going to improve our competence in the identification of new enzymatic targets, application of natural products and their synthetic analogues, biopharmaceuticals, antisense, and peptide antibiotics as antibacterials, as well as experience on biofilm formation and quorum sensing molecules as targets for new antibacterial therapies. In doing so, we will learn from our advanced foreign partners: the University of Antwerp, the University of Copenhagen, the University of Florence, and the University of Helsinki.

For further information, please contact Paula Kiuru. 


Sustainable Drug Discovery and Development with End-of-Life Yield

The environmental impacts of pharmaceuticals are a growing global problem. Whilst societies become increasingly urbanized and the world population grows in size and age, the use of pharmaceuticals and thus the chemical burden upon the environment increases. Emissions are produced throughout a pharmaceutical’s life cycle, from development to production, consumption and disposal.

SUDDEN is a research project that aims at reducing the environmental hazards related to the life cycle of pharmaceuticals. The project’s other objective is to enhance the sustainability of the pharmaceutical industry. We wish to create possibilities for sustainable growth by solving environmental issues related to the life cycle of pharmaceuticals. Moreover, SUDDEN will develop tools, solutions and policy recommendations which will create possibilities for sustainable growth by solving environmental issues in the life-cycle of a pharmaceutical. The SUDDEN project is funded by the Strategic Research Council of the Academy of Finland 2018-2023, after which the project will continue as SUDDEN Forum.

The project is carried out by the University of Helsinki, University of Eastern Finland, Lappeenranta-Lahti University of Technology LUT, Aalto University, Finnish Environment Institute and Demos Helsinki.

For further information, please contact Jari Yli-Kauhaluoma.

Towards Improved Parkinson's Disease Treatment

Levodopa (L-dopa) is the primary drug for managing symptoms of Parkinson's disease (PD). However, its effectiveness varies among individuals due to degradation into dopamine before reaching the brain, primarily through intestinal and peripheral metabolism. This metabolism diminishes therapy benefits while increasing undesirable side effects. Consequently, blocking these metabolic pathways presents a promising strategy to enhance L-dopa's efficacy for improved PD treatment. Therefore, the main objective of this project is to discover novel dual-targeting inhibitors of enzymes involved in L-dopa metabolism.

For further information, please contact Jayendra Patel. 


Transforming into a sustainable European pharmaceutical sector

Pharmaceuticals comprise a wide variety of chemical compounds designed to guarantee safe and effective therapies. The active pharmaceutical ingredients (APIs) are those that deliver the beneficial health effects experienced by the patients. The goal of the project is to develop more sustainable and greener APIs that simultaneously reduce the environmental footprint and the dependence on third countries for API production. The EU-funded TransPharm project will deliver digital tools and guidelines, also based on artificial intelligence, for the development of greener pharmaceutical products and APIs, as well as models to judge their impact. The result will be a more independent and competitive European pharmaceutical industry, which can ensure the timely delivery of sustainable and green therapeutics.

For further information, please contact Jari Yli-Kauhaluoma or Paula Kiuru.