GPR84 is a medium chain free fatty acid-binding G-protein-coupled receptor associated with inflammatory and fibrotic diseases. As the only reported antagonist of GPR84 (PBI-4050) that displays relatively low potency and selectivity, a clear need exists for an improved modulator. Structural optimization of GPR84 antagonist hit 1, identified through high-throughput screening, led to the identification of potent and selective GPR84 inhibitor GLPG1205 (36). Compared with the initial hit, 36 showed improved potency in a guanosine 5′-O-[γ-thio]­triphosphate assay, exhibited metabolic stability, and lacked activity against phosphodiesterase-4. This novel pharmacological tool allowed investigation of the therapeutic potential of GPR84 inhibition. At once-daily doses of 3 and 10 mg/kg, GLPG1205 reduced disease activity index score and neutrophil infiltration in a mouse dextran sodium sulfate-induced chronic inflammatory bowel disease model, with efficacy similar to positive-control compound sulfasalazine. The drug discovery steps leading to GLPG1205 identification, currently under phase II clinical investigation, are described herein.

Environmental contextAmmonium ion, an inorganic pollutant in agricultural land, can induce eutrophication, impacting on water quality. We investigate the adsorption of ammonium ion on surfactant-modified alumina and demonstrate highly efficient removal of ammonium ions by the alumina from two agricultural water samples. Adsorption mechanisms are also proposed based on adsorption isotherms, surface modification and the change in surface charge. AbstractThe adsorptive removal of ammonium ions (NH4+) from aqueous solution using surfactant-modified alumina (SMA) was investigated. The optimum NH4+ adsorption removal conditions on SMA were systematically studied and found to be pH 4, contact time 180min, adsorbent dosage 30mgmL–1 and ionic strength 1mM NaCl. The equilibrium concentration of NH4+ was measured by capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) and spectrophotometry. Surface modification of α-Al2O3 with the anionic surfactant sodium dodecyl sulfate (SDS) at high salt concentration induced a significant increase of removal efficiency. The change in surface charge and surface modification of α-Al2O3 by pre-adsorption of SDS and subsequent adsorption of NH4+ were evaluated by zeta potential measurements and Fourier-transform infrared spectroscopy. Under optimum adsorption conditions, NH4+ removal from two agricultural water samples achieved very high removal efficiencies of 99.5 and 96.5%. The adsorption of NH4+ onto SMA increases with decreasing NaCl concentration because desorption of SDS from the α-Al2O3 surface is minimised. Experimental results of NH4+–SMA adsorption isotherms at different ionic strengths can be represented well by a two-step adsorption model. Based on adsorption isotherms, surface charge effect and surface modification, we suggest that the adsorption mechanism of NH4+ onto SMA was mainly electrostatic attraction between cationic NH4+ and the negatively charged SMA surface.

In this study magnetic fluids were manufactured by the adsorption of chitosan (CS) and O-carboxymethyl chitosan (OCMCS) on Fe 3 O 4 nanoparticles to be used as hyperthermic thermoseeds. Fe 3 O 4 particles were characterized by physico-chemical methods such as: thermogravimetry analysis (TGA), x-ray diffraction (XRD), Raman spectrum, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and vibrating sample magnetometer (VSM). The SEM images and XRD patterns showed that the synthesized Fe 3 O 4 nanoparticles were of single phase and spherical shape with 10–15 nm in diameter. The VSM measurements showed that Fe 3 O 4 particles were superparamagnetic with saturation magnetization of 70 emu  g −1. The adsorbed layers of CS and OCMCS on the magnetite surface (Fe 3 O 4/CS) and (Fe 3 O 4/OCMCS) were confirmed by FTIR, Raman spectra and SEM. In the ac magnetic field of 80 Oe and 236 kHz, the saturation heating temperatures of the sample Fe 3 O 4/CS and Fe 3 O 4/OCMCS were 100 and 98 °C, respectively. At the same concentration of Fe 3 O 4 nanoparticles in suspension, the two magnetic fluids exhibited quite high heating capacity, with different behaviors of concentration dependence. The Fe 3 O 4/CS and Fe 3 O 4/OCMCS nanoparticles would serve as good thermoseeds for localized hyperthermia treatment of cancers.

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