Slava Ziegler

Slava Ziegler

Projektgruppenleiterin, Chemische Biologie

Research Concept

Bioactive small molecules are at the heart of disease therapies and have become indispensable tools to dissect and explore biological phenomena. But how are bioactive compounds actually identified? How do we gain the knowledge of their molecular targets and/or mode of action that will guides us to application areas in biological research or drug discovery?

Our lab develops and employs phenotypic assays to identify bioactive small molecules. Our aim is to identify modulators of various processes that contribute to tumorigenesis, e.g. developmental pathways, deregulated cellular energetics, oxidative stress and immune cell-assisted cancer cell elimination. In addition, we employ morphological profiling by means of the Cell painting assay to explore the biological activity of newly synthesized compounds in an unbiased manner, to subsequently predict a mode of action and to map them in the bioactivity space. For compounds with known target or mode of action, e.g. drugs or tool compounds, we use the Cell painting assay to link morphological changes to a mode of action and to uncover novel, not yet reported (off-) targets.

To achieve this goal, the developed assays are transferred to the Compound management and screening center (COMAS)in Dortmund for performing high-throughput screenings. We explore then the screening hits by means of diverse approaches and techniques:

  • Real-time kinetic monitoring of cancer cell growth and cell death using live-cell imaging
  • Metabolic flux analysis
  • Reporter gene assays
  • Structure-activity studies to guide the design of more potent derivatives and for the synthesis of affinity probes
  • Affinity-based chemical proteomics for target identification
  • Thermal proteome profiling for target deconvolution or validation
  • Proteome profiling for mode-of-action analysis

Over the last 10 years, we have established an extensive workflow for the confirmation of putative targets for small molecules and have applied it successfully in various projects:


Zimmermann TJ, Roy S, Martinez NE, Ziegler S, Hedberg C, Waldmann H (2013). Biology-oriented synthesis of a tetrahydroisoquinoline-based compound collection targeting microtubule polymerization. Chembiochem 14(3):295-300. 
doi: 10.1002/cbic.201200711. 

Tran TT, Gerding-Reimers C, Schölermann B, Stanitzki B, Henkel T, Waldmann H, Ziegler S (2014). Podoverine A--a novel microtubule destabilizing natural product from the Podophyllum species. Bioorg Med Chem 22(18):5110-6. 
doi: 10.1016/j.bmc.2014.01.039. 


Akbulut Y, Gaunt HJ, Muraki K, Ludlow MJ, Amer MS, Bruns A, Vasudev NS, Radtke L, Willot M, Hahn S, Seitz T, Ziegler S, Christmann M, Beech DJ & Waldmann H (2015). (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angew Chem Int Ed Engl 54(12):3787-3791. 
doi: 10.1002/anie.201411511. 


Kremer L, Schultz-Fademrecht C, Baumann M, Habenberger P, Choidas A, Klebl B, Kordes S, Schöler HJ, Sterneckert J, Ziegler S, Schneider G., Waldmann H (2017). Discovery of a Novel Hedgehog Signaling Pathway Inhibitor by Cell-based Compound Discovery and Target Prediction. Angew Chem Int Ed Engl 
doi: 10.1002/anie.201707394. 

Lee YC, Patil S, Golz C, Strohmann C, Ziegler S, Kumar K, Waldmann H (2017). A ligand-directed divergent catalytic approach to establish structural and functional scaffold diversity. Nat Commun 8:14043 
doi: 10.1038/ncomms14043.


Schneidewind T, Kapoor S, Garivet G, Karageorgis G, Narayan R, Vendrell-Navarro G, Antonchick AP, Ziegler S, Waldmann H(2019). The Pseudo Natural Product Myokinasib Is a Myosin Light Chain Kinase 1 Inhibitor with Unprecedented Chemotype. Cell Chem Biol
doi: 10.1016/j.chembiol.2018.11.014. 


Kremer L, Hennes E, Brause A, Ursu A, Robke L, Matsubayashi HT, Nihongaki Y, Flegel J, Mejdrová I, Eickhoff J, Baumann M, Nencka R, Janning P, Kordes S, Schöler HR, Sterneckert J, Inoue T, Ziegler S, Waldmann H (2019). Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß. Angew Chem Int Ed Engl
doi: 10.1002/anie.201907632. 


Karageorgis G, Reckzeh ES, Ceballos J, Schwalfenberg M, Sievers S, Ostermann C, Pahl A, Ziegler S, Waldmann H (2018). Chromopynones are pseudo natural product glucose uptake inhibitors targeting glucose transporters GLUT-1 and -3. Nat Chem 
doi: 10.1038/s41557-018-0132-6.

Reckzeh ES, Karageorgis G, Schwalfenberg M, Ceballos J, Nowacki J, Stroet MCM, Binici A, Knauer L, Brand S, Choidas A, Strohmann C, ZieglerS, Waldmann H (2019). Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth Cell Chemical Biology 

Ceballos J, Schwalfenberg M, Karageorgis G, Reckzeh ES, Sievers S, Ostermann C, Pahl A, Sellstedt M, Nowacki J, Carnero Corrales M, Wilke J, Laraia L, Tschapalda K, Metz M, Sehr DA, Brand S, Winklhofer K, Janning P, Ziegler S, Waldmann H (2019). Synthesis of Indomorphan Pseudo Natural Product Inhibitors of Glucose Transporters GLUT-1 and -3. Angew Chem Int Ed Engl 
doi: 10.1002/anie.201909518. 

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