Pretze, Marc published the artcileSynthesis, radiolabelling and initial biological characterisation of 18F-labelled xanthine derivatives for PET imaging of Eph receptors, Safety of 1-Methylurea, the main research area is fluorine 18 xanthine derivative preparation imaging Eph receptor cancer.
Eph receptor tyrosine kinases, particularly EphA2 and EphB4, represent promising candidates for mol. imaging due to their essential role in cancer progression and therapy resistance. Xanthine derivatives were identified to be potent Eph receptor inhibitors with IC50 values in the low nanomolar range (1-40 nm). These compounds occupy the hydrophobic pocket of the ATP-binding site in the kinase domain. Based on lead compound 1, we designed two fluorine-18-labeled receptor tyrosine kinase inhibitors ([18F]2/3) as potential tracers for positron emission tomog. (PET). Docking into the ATP-binding site allowed us to find the best position for radiolabelling. The replacement of the Me group at the uracil residue ([18F]3) rather than the Me group of the phenoxy moiety ([18F]2) by a fluoropropyl group was predicted to preserve the affinity of the lead compound 1. Herein, we point out a synthesis route to [18F]2 and [18F]3 and the resp. tosylate precursors as well as a labeling procedure to insert fluorine-18. After radiolabelling, both radiotracers were obtained in approx. 5% radiochem. yield with high radiochem. purity (>98%) and a molar activity of >10 GBq μmol-1. In line with the docking studies, first cell experiments revealed specific, time-dependent binding and uptake of [18F]3 to EphA2 and EphB4-overexpressing A375 human melanoma cells, whereas [18F]2 did not accumulate at these cells. Since both tracers [18F]3 and [18F]2 are stable in rat blood, the novel radiotracers might be suitable for in vivo mol. imaging of Eph receptors with PET.
Organic & Biomolecular Chemistry published new progress about EphA2 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 598-50-5 belongs to class isoquinoline, name is 1-Methylurea, and the molecular formula is C2H6N2O, Safety of 1-Methylurea.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem