Regulation of dual leucine zipper kinase activity through its interaction with calcineurin.

Hyperglycemia enhancing the intracellular levels of reactive oxygen species (ROS) contributes to dysfunction and progressive loss of beta cells and thereby to diabetes mellitus. The oxidation sensitive calcium/calmodulin dependent phosphatase calcineurin promotes pancreatic beta cell function and survival whereas the dual leucine zipper kinase (DLK) induces apoptosis. Therefore, it was studied whether calcineurin interferes with DLK action.

Dual leucine zipper kinase (MAP3K12) modulators: a patent review (2010-2015).

Introduction: The dual leucine zipper kinase (DLK, MAP3K12) is essential for neuronal development and has been shown to mediate axon regeneration. On the other hand, DLK is involved in the pathogenesis of neurodegenerative disease and diabetes mellitus. Several patents have been published claiming to modulate or inhibit DLK by various approaches including ATP competitive inhibitors.

Salvage Completion Pancreatectomies as Damage Control for Post-pancreatic Surgery Complications: A Single-Center Retrospective Analysis.

Background: Post-pancreatic surgical morbidity is frequent but often manageable by less invasive means than re-operation. Yet, some complications can become hazardous and life threatening. Herein, the results of a completion pancreatectomy (CP) to cope with severe post-operative pancreatic fistulas (POPF) and bleeding complications after major pancreatic resections for suspected pancreatic malignancy are presented.

3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles are selective inhibitors of Plasmodium falciparum glycogen synthase kinase-3.

Plasmodium falciparum is the infective agent responsible for malaria tropica. The glycogen synthase kinase-3 of the parasite (PfGSK-3) was suggested as a potential biological target for novel antimalarial drugs. Starting from hit structures identified in a high-throughput screening campaign, 3,6-diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles were discovered as a new class of PfGSK-3 inhibitors.

Dual IGF-1R/SRC inhibitors based on a N'-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide structure.

The N'-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide motif was identified as a novel scaffold for the development of kinase inhibitors. Derivatives with a biphenyl element attached to the hydrazide structure proved to be submicromolar dual inhibitors of the cancer-related kinases IGF-1R and SRC. One of the most potent kinase inhibitors of the series produced a selective growth inhibition in a panel of cultivated cancer cell lines.