Discovery of Novel Symmetrical 1,4-Dihydropyridines as Inhibitors of Multidrug-Resistant Protein (MRP4) Efflux Pump for Anticancer Therapy

Despite the development of targeted therapies in cancer, the problem of multidrug resistance (MDR) is still unsolved. Most patients with metastatic cancer die from MDR. Transmembrane efflux pumps as the main cause of MDR have been addressed by developed inhibitors, but early inhibitors of the most prominent and longest known efflux pump P-glycoprotein (P-gp) were disappointing. Those inhibitors have been used without knowledge about the expression of P-gp by the treated tumor. Therefore the use of inhibitors of transmembrane efflux pumps in clinical settings is reconsidered as a promising strategy in the case of the respective efflux pump expression. We discovered novel symmetric inhibitors of the symmetric efflux pump MRP4 encoded by the ABCC4 gene. MRP4 is involved in many kinds of cancer with resistance to anticancer drugs. All compounds showed better activities than the best known MRP4 inhibitor MK571 in an MRP4-overexpressing cell line assay, and the activities could be related to the various substitution patterns of aromatic residues within the symmetric molecular framework. One of the best compounds was demonstrated to overcome the MRP4-mediated resistance in the cell line model to restore the anticancer drug sensitivity as a proof of concept.     

Investigations of Solid State Dynamics at the NRSSR Beamline at PETRA II. An Overview

The present status of the new nuclear resonance beamline PETRA 1 at HASYLAB, DESY, Hamburg is described. Besides an overview of the experimental setup some examples of recent experiments are given. Those cover the main applications, i.e., inelastic scattering from iron alloys and quasielastic scattering from glass-forming liquids. This revised version was published online in August 2006 with corrections to the Cover Date.     

Schwefeleisen als L?throhrreagens

Ohne Zusammenfassung     

On the Zeros of Orthogonal Polynomials: The Elliptic Case

Constructive Approximation - Let E = [–1, α] \cup [β, 1], –1 &;lt; α &;lt; β &;lt; 1, and let (pn) be orthogonal on E with respect to the weight function...     

Moderate Deviations for Longest Increasing Subsequences: The Lower Tail

We derive a moderate deviation principle for the lower tail probabilities of the length of a longest increasing subsequence in a random permutation. It refers to the regime between the lower tail large deviation regime and the central limit regime. The present article together with the upper tail moderate deviation principle in Ref. 12 yields a complete picture for the whole moderate deviation regime. Other than in Ref. 12, we can directly apply estimates by Baik, Deift, and Johansson, who obtained a (non-standard) Central Limit Theorem for the same quantity.