Highly selective CYP1B1 inhibitors have potential in the treatment of hormone-induced breast and prostate cancers. Mimicry of potent and selective CYP1B1 inhibitors, α-naphthoflavone and stilbenes, revealed that two sets of hydrophobic clusters suitably linked via a polar linker could be implanted into a new scaffold 'biphenyl ureas' to create potentially a new class of CYP1B1 inhibitors. A ser...

UNLABELLED (11)C-LY2795050 is a novel κ-selective antagonist PET tracer. The in vitro binding affinities (Ki) of LY2795050 at the κ-opioid (KOR) and μ-opioid (MOR) receptors are 0.72 and 25.8 nM, respectively. Thus, the in vitro KOR/MOR binding selectivity is about 36:1. Our goal in this study was to determine the in vivo selectivity of this new KOR antagonist tracer in the monkey. METHODS To...

In the recent collection of articles in Perspectives on: Ion selectivity, several authors summarized the current state of knowledge on ion channel selectivity, predominated by experimental and theoretical approaches to understanding K + /Na + discrimination of passive ion channels. Considerable insight has been gained by complementary analyses of crystal structures as well as by molecular simul...

In this review, we present a summary of how computer modeling has been used in the development of covalent-modifier drugs. Covalent-modifier drugs bind by forming a chemical bond with their target. This covalent binding can improve the selectivity of the drug for a target with complementary reactivity and result in increased binding affinities due to the strength of the covalent bond formed. In...

Directional selectivity, in which neurons respond strongly to an object moving in a given direction but weakly or not at all to the same object moving in the opposite direction, is a crucial computation that is thought to provide a neural correlate of motion perception. However, directional selectivity has been traditionally quantified by using the full spike train, which does not take into acc...

Novel C2-symmetric diiminosphosphoranes and diketimines are useful ligands for Pd-and Cu-catalyzed C±C bond forming reactions, Angermund's molecular modeling based on accessible molecular surface serving as a guide in predicting catalyst activity. The ®rst highly enantioselective diphosphites as ligands in Rh-catalyzed hydrogenation are also described, the selectivity principle being based on i...

The ability to represent and recognize naturally occuring sounds such as speech depends not only on spectral analysis carried out by the subcortical auditory system but also on the ability of the cortex to bind spectral information over time. In primates, these temporal binding processes are mirrored as selective responsiveness of neurons to species-specific vocalizations. Here, we used computa...

Co-precipitated Cu-MgO catalysts were prepared and evaluated for the gas-phase hydrogenation of furfural. The effect of heating rate at the calcination step was studied by comparing the performance of three catalysts prepared via the same procedure but calcined at different heating rates. The results established that altering the heating rate could influence the structural properties of the cat...

The binding selectivity of the M(phen)(edda) (M=Cu, Co, Ni, Zn; phen=1,10-phenanthroline, edda=ethylenediaminediacetic acid) complexes towards ds(CG)(6), ds(AT)(6) and ds(CGCGAATTCGCG) B-form oligonucleotide duplexes were studied by CD spectroscopy and molecular modeling. The binding mode is intercalation and there is selectivity towards AT-sequence and stacking preference for A/A parallel or d...

Many drug candidates fail in clinical development due to their insufficient selectivity that may cause undesired side effects. Therefore, modern drug discovery is routinely supported by computational techniques, which can identify alternate molecular targets with a significant potential for cross-reactivity. In particular, the development of highly selective kinase inhibitors is complicated by ...