Pharmacophores are associated with binding sites of proteins and characterize the arrangement of chemical and physical features that govern the modes of interactions of different ligands within the binding sites. Methods designed to infer pharmacophores computationally have been successfully applied in drug discovery pipelines.

Virtual high-throughput screening (HTS), lead optimization, Selleck Cediranib and de novo drug design are just a few areas in which pharmacophores are actively used. This review surveys different computational methods to elucidate pharmacophores and discuss their utilization in drug discovery applications. Drug Dev Res 72: 17-25, 2011. (C) 2010 Wiley-Liss, Inc.”
“Preterm birth (PTB), defined as any birth occurring before 37 weeks of gestation, occurs in only 12% of all births, yet accounts for nearly half of long-term neurological morbidity, and 60%-80% of perinatal mortality. The single most common cause of PTB is intrauterine infection. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that is both upregulated by

inflammatory cytokines and capable of increasing myometrial smooth muscle tone. We hypothesized, therefore, that ET-1 is a critical component of the parturition cascade in the setting of infection-associated JSH-23 research buy PTB. In our previous work, we have shown that blockade of ET-I synthesis through the use of the metalloproteinase inhibitor phosphoramidon results in control of preterm labor. In the current work, we showed that blockade of ET-I action with 5-50 mg/kg i.p. 3-(3-carboxybenzyl)-1-((6-ethylbenzo[d][1,3]dioxol-5-yl)methyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxylic acid (HJP272), a putative novel selective ETA-receptor antagonist (IC50, 70 nmol/L), prevents PTB induced with AZD5153 in vivo up to 50 mg/kg of i.p. lipopolysaccharide in a mouse model. This is the first report, to our knowledge, of control of infection-associated PTB with a specific ETA-receptor antagonist. The identification of a novel effective therapy for PTB could have important clinical implications.”
“PURPOSE. To assess the effects

of intravitreal bevacizumab injections in the treatment of subfoveal choroidal neovascularization (CNV) associated with pattern dystrophy (PD) of the retinal pigment epithelium.\n\nMETHODS. The study was a prospective, nonrandomized, openlabel, interventional clinical trial in which 12 patients were prospectively enrolled. Patients with a diagnosis of PD complicated by subfoveal CNV were considered for the study. All patients underwent a complete ophthalmic examination, including ETDRS visual acuity measurement, electroretinogram, electrooculogram, optical coherence tomography, and fluorescein angiography. The treatment protocol began with a loading dose of three consecutive injections at 1-month intervals, followed by injections administered as needed, according to OCT parameters and angiographic features observed during a 24-month follow-up period.