Disputas: Vegard Torp Lien

Ph.d.-kandidat Vegard Torp Lien ved Farmasøytisk institutt, Det matematisk-naturvitenskapelige fakultet, vil forsvare avhandlingen "Development of diagnostic and therapeutic tools for MET and associated targets in cancer" for graden Philosophiae Doctor.

Bildet kan inneholde: klær, ansikt, hår, hake, panne.

Prøveforelesning - tid og sted

07.02. 09.15, Auditorium 3, Helga Eng

PET imaging of bacterial infections - State of the art and future perspectives

 

Kreeringssammendrag

Nye legemidler og bedre diagnostikk er nødvendig for å forbedre prognosen for kreftsykdommer. I denne avhandlingen har kjemisk legemiddeldesign og syntese blitt brukt for å undersøke hvordan småmolekylære forbindelser kan blokkere eller avbilde tyrosin kinasen MET i ulike krefttyper. Videre har en ny strategi for den samtidige inhiberingen av MET og signalveien WNT blitt introdusert.   

 

Hovedfunn

The kinase MET in the treatment and diagnosis of cancer

 

Although there has been a surge in novel drug substances for use in cancer treatment, innovations are still needed. In this respect, protein kinases are attractive drug targets as they are often dysregulated in cancer. In this thesis, medicinal chemistry based drug design and synthesis have been used to provide novel molecules with both therapeutic and diagnostic applications towards the tyrosine kinase MET. A series of 6-substituted quinolines were synthesized and several of the molecules were more potent inhibitors of MET than cabozantinib, a clinically approved MET inhibitor. As simultaneous inhibition of several targets may provide improved therapeutic effects, the reported work explored the design and synthesis of the first low-molecular dual inhibitors of MET and the signalling pathway WNT. Several dual inhibitors were identified which provide a novel scaffold amendable to optimization for the generation of clinically useful molecules for use in cancer therapy.

 

Molecular imaging of MET was performed with the selective [18F]PF04217903 and the non-selective [18F]cabozantinib using positron emission tomography (PET). In prostate cancer xenografted mice, the tumor was visualized with [18F]cabozantinib, however slow wash-out and high unspecific binding makes it less suitable as a PET imaging probe. [18F]PF04217903 displayed more favourable characteristics and may be a promising tracer for the imaging of MET.

 

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Publisert 28. jan. 2020 08:12 - Sist endret 6. feb. 2020 07:59