Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains
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AMP-activated protein kinase (AMPK) is a fundamental enzyme that controls energy homeostasis, through orchestrating the cellular response to a reduction in energy availability. Under conditions of cellular energy stress AMPK senses the decrease in ATP leve ...
Targeted cancer therapy is a very promising concept; however, small molecule inhibitors only exist for a limited number of oncoproteins and resistance development limits their clinical use. Different engineered non-antibody scaffolds are being explored to ...
Bacteriophages of the myoviridae family, R-type pyocin, Photorhabus virulence cassette (PVC), Serratia antifeeding prophage (Afp) and type 6 secretion system (T6SS) form a class of contractile injection systems that share common structural and functional c ...
In principle, a major goal in drug development is to design a high-affinity compound with an appropriate pharmacological response, which requires understanding of physical processes underlying the drug-target interaction, affinity and specificity. This dru ...
Chiral lactam 2 and three chiral 3-amino alcohols 3-5 have been synthesized and characterized by Sspectroscopic techniques. Regioselective ring opening reaction of chiral styrene oxide by an amine nucle-ophile was confirmed by X-ray diffraction data. Ligan ...
Because signaling mediated by the transcription factor nuclear factor kappa B (NF-kappa B) is initiated by ligands and receptors that can undergo internalization, we investigated how endocytic trafficking regulated this key physiological pathway. We deplet ...
Human purinergic Gprotein-coupled receptor P2Y(1) (P2Y(1)R) is activated by adenosine 5'-diphosphate (ADP) to induce platelet activation and thereby serves as an important antithrombotic drug target. Crystal structures of P2Y(1)R revealed that one ligand ( ...
Known gamma-secretase inhibitors or modulators display an undesirable pharmacokinetic profile and toxicity and have therefore not been successful in clinical trials for Alzheimer's disease (AD). So far, no compounds from natural products have been identifi ...
The transduction of extracellular signals through signaling pathways that culminate in a transcriptional response is central to many biological processes. However, quantitative relationships between activities of signaling pathway components and transcript ...
Better antibiotics capable of killing multi-drug-resistant Mycobacterium tuberculosis are urgently needed. Despite extensive drug discovery efforts, only a few promising candidates are on the horizon and alternative screening protocols are required. Here, ...