Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, has attracted interest as a target for pharmacological intervention in malignant diseases. Here, we describe BI 853520, a novel ATP-competitive inhibitor distinguished by high potency and selectivity. In vitro, the compound inhibits FAK autophosphorylation in PC-3 prostate carcinoma cells with an IC of 1 nmol/L and blocks anchorage-independent proliferation of PC-3 cells with an EC of 3 nmol/L, whereas cells grown in conventional surface culture are 1000-fold less sensitive.
View Article and Find Full Text PDFRett syndrome is an X chromosome-linked neurodevelopmental disorder associated with cognitive impairment, motor dysfunction and breathing irregularities causing intermittent hypoxia. Evidence for impaired mitochondrial function is also accumulating. A subunit of complex III is among the potentially dys-regulated genes, the inner mitochondrial membrane is leaking protons, brain ATP levels seem reduced, and Rett patient blood samples confirm increased oxidative damage.
View Article and Find Full Text PDFThe tetraspanin CD37 is widely expressed in B-cell malignancies and represents an attractive target for immunotherapy with mAbs. We have chimerized a high-affinity mouse Ab to CD37 and engineered the CH2 domain for improved binding to human Fcγ receptors. The resulting mAb 37.
View Article and Find Full Text PDFTo implement the European Water Framework Directive (WFD) into German law, measures have to be taken to reduce the unacceptably high nutrient input into rivers. To identify the most effective measures, the sources and pathways of nutrient emissions into rivers have to be quantified. Therefore, the MONERIS model is applied, which quantifies nutrients emissions into river basins, via various point and diffuse pathways, as well as nutrient load in rivers.
View Article and Find Full Text PDFObjectives: The purpose of this study was to evaluate the extent to which various commercially available gadolinium-containing contrast-enhancing (CE) agents can interfere with the measurement of calcium levels by currently used laboratory methods, suggesting (spurious) hypocalcemia or hypercalcemia with a potential risk for the patient.
Materials And Methods: Serum and plasma from healthy volunteers were spiked with various concentrations of 4 marketed CE agents. The calcium concentration was measured by widely used laboratory methods: the colorimetric systems Cobas Mira and Vitros 950 analyzer.