c-Jun N-terminal Kinases (JNKs) represent valuable targets in the development of new therapies. Present on the surface of JNK is a binding pocket for substrates and the scaffolding protein JIP1 in close proximity to the ATP binding pocket. We propose that bi-dentate compounds linking the binding energies of weakly interacting ATP and substrate mimetics could result in potent and selective JNK inhibitors. We describe here a bi-dentate molecule, 19, designed against JNK. 19 inhibits JNK kinase activity (IC50 = 18 nM; Ki = 1.5 nM) and JNK/substrate association in a displacement assay with a substrate peptide (compound 20; IC50 = 46 nM; Ki = 2 nM). Our data demonstrate that 19 targets for the ATP and substrate-binding sites on JNK concurrently. Finally, compound 19 not only inhibits JNK in a variety of cell-based experiments, but it elicits also in vivo activity where it is shown to improve glucose tolerance in diabetic mice.

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The estimation of wildlife populations is an issue currently being solved at workplaces on many levels. Knowledge of wildlife population and localization is not only very important for reducing damage to agricultural and forest growth, which arises from the local overgrowth of certain animal species, but also for the protection of endangered species of animals and plants.The article presents the results of a research carried out during 2017 as the first partial objective of a complex automated wildlife estimation project, namely the recognition of game in a free landscape without vegetation cover from an UAV (unmanned aerial vehicle). The paper describes a method of finding game animals in a selected area and identifies problems with the recognition of the animals hiding in the vegetation. These results play an important role in solving the overall complex problem of automated game recognition.