Direct stimulation of angiotensin II type 2 receptor reduces nitric oxide production in lipopolysaccharide treated mouse macrophages.

The angiotensin II type 2 receptor (AT) is upregulated after tissue damage and mediates protective functions in the renin-angiotensin-aldosterone system (RAAS). One of these is to inhibit inducible nitric oxide synthase (iNOS) in activated macrophages. In the present study, we assessed the effect of AT receptor ligands on nitric oxide production in murine macrophages as a potential assay to determine the functional activity of an AT receptor ligand.

Author Correction: Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Series of Analogues to the ATR Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode.

We here report on our continued studies of ligands binding to the promising drug target angiotensin II type 2 receptor (ATR). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small substituents to the phenyl ring of the known selective nonpeptide ATR antagonist , generating small but significant shifts in ATR affinity.

Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.

With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells.

A convenient transesterification method for synthesis of AT2 receptor ligands with improved stability in human liver microsomes.

A series of ATR ligands have been synthesized applying a quick, simple, and safe transesterification-type reaction whereby the sulfonyl carbamate alkyl tail of the selective ATR antagonist C38 was varied. Furthermore, a limited number of compounds where acyl sulfonamides and sulfonyl ureas served as carboxylic acid bioisosteres were synthesized and evaluated. By reducing the size of the alkyl chain of the sulfonyl carbamates, ligands 7a and 7b were identified with significantly improved in vitro metabolic stability in both human and mouse liver microsomes as compared to C38 while retaining the ATR binding affinity and ATR/ATR selectivity.

Coalescence of particle-laden drops with a planar oil-water interface.

The coalescence mechanism of a particle-laden drop resting at an oil-water interface has been studied. Two mechanisms for drop coalescence are observed; (i) complete coalescence, in which the drop experiences total coalescence in one event, and (ii) partial coalescence, where a drop is observed to separate during coalescence, producing a smaller secondary drop that rebounds and comes to rest at the planar oil-water interface. For particle-laden drops of approximately 4mm in diameter, we show the critical condition for partial to complete coalescence to be dependent on the particle concentration, and the interparticle interaction energy.