RX-207, a Small Molecule Inhibitor of Protein Interaction with Glycosaminoglycans (SMIGs), Reduces Experimentally Induced Inflammation and Increases Survival Rate in Cecal Ligation and Puncture (CLP)-Induced Sepsis.

The fused quinazolinone derivative, RX-207, is chemically and functionally related to small molecule inhibitors of protein binding to glycosaminoglycans (SMIGs). Composed of a planar aromatic amine scaffold, it inhibits protein binding to glycosaminoglycans (GAGs). RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%).

Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

Objective And Design: Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease.

Materials: The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111.

Small molecule inhibitors of protein interaction with glycosaminoglycans (SMIGs), a novel class of bioactive agents with anti-inflammatory properties.

Background: Small molecule inhibitors of biologically important protein-glycosaminoglycan (GAG) interactions have yet to be identified.

Methods: Compound libraries were screened in an assay of L-selectin-IgG binding to heparin (a species of heparan sulfate [HS-GAG]). Hits were validated, IC-50s established and direct binding of hits to HS-GAGs was investigated by incubating compounds alone with heparin.

[Maternal-fetal transmission of HIV: preventive measures and prenatal care].

HIV can be transmitted to foetus during pregnancy, labour, and breastfeeding. An estimated 600,000 newborns acquired HIV each year through mother to fetus transmission. Without preventive interventions, approximately 25% of infants born to HIV positive mothers contract the virus.

Human chorionic gonadotropin (hCG) treatment in cryptorchidism.

One hundred twenty-eight prepubertal boys, ages 1-12 years, were referred to our institute because of uni- or bilateral cryptorchidism. Patients with mobile (retractile) testes were not included in the study. They were treated with human chorionic gonadotrophin (hCG, Pregnyl-Teva) twice weekly for five consecutive weeks by the following doses; 1-4 years (n = 53) - 250 U X 10; 4-7 years (n = 51) - 500 U X 10; 7-12 years (n = 24) - 1000 U X 10;i.