Development of novel cytotoxic payloads for extracellular-targeted drug-conjugates (EDCs)

Extracellular-targeted drug-conjugates of biological sensor molecules with a high affinity for a specific cancer biomarker on cell surfaces and highly potent cytotoxins are an emergent strategy to treat cancer. Due to a higher selectivity compared to conventional chemotherapeutics, these conjuagtes show a significant lower systemic toxicity and bigger therapeutic window.

We aim the synthesis of novel cytotoxic payloads with new mode of action for the development of extracellular-targeted drug-conjugates (EDCs) for cancer treatment. We focus on a novel strategy to synthesis non-toxic natural product derived prodrugs, which are envisaged to undergo an toxification cascade upon intracellular linker cleavage. We furthermore conjugate appropiate payloads to sensor molecules and biologically evaluate the resulting conjugates together with our collaboration partners. 

Selected publications:

Comprehensive cell biological investigation of cytochalasin B derivatives with distinct activities on the actin network, M. D. Kagho, K.Schmidt, C. Lambert, T. Kaufmann, L. Jia, J. Faix, K. Rottner, M. Stadler, T. Stradal,* P. Klahn*, J. Nat. Prod. 2024, 87, 2421; ChemRxiv 2024, DOI: 10.26434/chemrxiv-2024-qlj57-v2.

The Nuclear Export Inhibitor Aminoratjadone is a Potent Effector in Extracellular-Targeted Drug Conjugates, P. Klahn*, V. Fetz, A. Ritter, W. Collisi, B. Hinkelmann, T. Arnold, W. Tegge, K. Rox, S. Hüttel, K. I. Mohr, J. Wink, M. Stadler, J. Wissings, L. Jänsch, M. Brönstrup*, Chem. Sci.  2019, 10, 5197-5210. 

New targeted cytotoxic Ratjadone derivatives and conjugates thereof, P. Klahn, M. Brönstrup, V. Fetz, S. Hüttel, K. I. Mohr, W. Tegge, W. Collisi, 2019, WO2019/03028431 A1