Paul van Slobbe

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BACKGROUND Tyrosine kinase inhibitors (TKIs) have experienced a tremendous boost in the last decade, where more than 15 small molecule TKIs have been approved by the FDA. Unfortunately, despite their promising clinical successes, a large portion of patients remain unresponsive to these targeted drugs. For non-small cell lung cancer (NSCLC), the(More)
The discovery and increased understanding of tumor targets has led to the development and approval of 12 small molecule tyrosine kinase inhibitors (TKIs). Despite tremendous efforts in TKI development, treatment efficacies with these therapeutics are still too low and improvements require a personalized medicine approach. Positron emission tomography (PET)(More)
INTRODUCTION Tyrosine kinase inhibitors (TKIs) are very attractive targeted drugs, although a large portion of patients remains unresponsive. PET imaging with EGFR targeting TKIs ([(11)C]erlotinib and [(18)F]afatinib) showed promise in identifying treatment sensitive tumors. The aim of this study was to synthesize two anti-angiogenic TKI tracers,(More)
INTRODUCTION Afatinib is an irreversible ErbB family blocker that was approved for the treatment of EGFR mutated non-small cell lung cancer in 2013. Positron emission tomography (PET) with fluorine-18 labeled afatinib provides a means to obtain improved understanding of afatinib tumor disposition in vivo. PET imaging with [(18)F]afatinib may also provide a(More)
A litter of pups: The synthesis and in vitro evaluation of new Pup-based fluorogenic substrates for Dop, the mycobacterial depupylase, are described. A full-length Pup-amidomethylcoumarin conjugate as well as an amino-terminus-truncated analogue exhibited high sensitivity and specificity towards hydrolysis by Dop. The substrates developed here might find(More)
A convenient trans-selective one-pot synthesis of tetrafunctionalized 2-imidazolines is described. Our approach to these valuable heterocyclic scaffolds involves a formal 1,3-dipolar cycloaddition between nitrile ylides or nitrilium triflates and imines. A detailed experimental study in combination with a high-level computational exploration of reaction(More)
Over the last decade kinase inhibitors have witnessed tremendous growth as anti-cancer drugs. Unfortunately, despite their promising clinical successes, a large portion of patients does not benefit from these targeted therapeutics. Vemurafenib is a serine/threonine kinase inhibitor approved for the treatment of melanomas specifically expressing the(More)
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