Co-Mentor: Robert Grotzfeld, PhD
Global Discovery Chemistry
A priority research area for our New Modalities Group is to evaluate and further develop a variety of techniques for the targeted delivery of novel drug molecules to diseased tissue. The ultimate goal is to apply the most effective and innovative targeting strategies to the next generation of medicines, achieving excellent efficacy and vastly superior safety profiles compared to current treatments, thus bringing the maximum benefit to patients. We have developed expertise in targeted delivery of cytotoxic compounds into tumor tissues in the context of antibody-drug-conjugates (ADCs). Building on this experience, we will now look beyond ADCs and investigate the opportunities and limitations of passive targeted delivery approaches relying on the EPR (enhanced permeability and retention) effect. Drawing from our extensive experience in linker chemistry, we aim at designing the next generation of tissue targeting systems which would release drugs only at the desired site of action, thus maximizing their therapeutic window.
One aspect of this is to evaluate dendrimers as carriers for drug delivery. Dendrimers represent a flexible and modular approach that will enable the exploration of specific drug release mechanisms in combination with tissue-targeting modalities. We aim to develop novel linkers and dendrimer scaffolds and evaluate biological activity of the resulting constructs in vivo.
Optimization of a dibenzodiazepine hit to a potent and selective allosteric PAK1 inhibitor.
Karpov AS, Amiri P, Bellamacina C, Bellance M-H, Breitenstein W, Daniel D, Denay R, Fabbro D, Fernandez C, Galuba I, Guerro-Lagasse S, Gutmann S, Hinh L, Jahnke W, Klopp J, Lai A, Lindvall MK, Ma S, Möbitz H, Pecchi S, Rummel G, Shoemaker K, Trappe J, Voliva C, Cowan-Jacob SW, Marzinzik AL.
ACS Med. Chem. Lett. 2015 May 22; 6 (7): 776–781.
Synthesis of new bulky bis(pyrazolyl)methane carboxylate (heteroscorpionate) ligands and their complexes with iron, manganese and nickel.
Jones MW, Baldwin JE, Cowley AR, Dilworth JR, Karpov A, Smiljanic N, Thompson AL, Adlington RM.
Dalton Trans. 2012 Dec 14; 41 (46): 14068–14086.
Concise syntheses of meridianins by carbonylative alkynylation and a four-component pyrimidine synthesis.
Karpov AS, Merkul E, Rominger F, Müller TJ.
Angew. Chem. Int. Ed. 2005 Oct 28; 44(42): 6951–6956.
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