Two GnRH-mitoxantrone Conjugates, Con-3 and Con-7, Target Endometrial Cancer Cells.

Introduction: Endometrial cancer is one of the most common gynecological malignancies. Endometrial cancer cells express the gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R). Among the various therapeutic approaches for the treatment of endometrial cancer is the use of GnRH conjugates, such as the AN-152, created by linking the [D-Lys6] GnRH with the cytotoxic doxorubicin through an ester bond.

Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells.

The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7.

Reductions of food intake and body weight in diet-induced obese rats following chronic treatment with a monomeric peptide multiagonist.

Introduction: While therapies based on endogenous gut peptides such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have been compelling therapeutic agents for obesity and type 2 diabetes (T2D), only a few have achieved long-term weight loss and all have shown significant side-effects, including nausea/malaise and gastrointestinal ailments.

Objective: As the pathophysiology of obesity is driven by dysregulation of multiple, inter-related, pathways, we tested a novel peptide targeting multiple receptors of complementary neurocircuits regulating the controls of energy balance.

Methods: Response to daily injections of GEP44, a GLP-1R and neuropeptide Y1R and Y2R receptor (Y1R/Y2R) triple agonist was tested vs.

A case of babesiosis in a returning traveller.

Unlabelled: Human babesiosis data in Africa is scarce. The clinical presentation and parasite morphology mimics falciparum malaria infection. Diagnostic confirmation is informed by adequate history and communication with the laboratory to activate appropriate testing.

Corrination mitigates peptide aggregation as exemplified for Glucagon.

Pharmaceutical development of glucagon for use in acute hypoglycemia has proved challenging, due in large part to poor solubility, poor stability and aggregate formation. Herein, we describe highly soluble, low aggregating, glucagon conjugates generated through use of the commercially available vitamin B precursor dicyanocobinamide ('corrination'), which retain full stimulatory action at the human glucagon receptor. The modified glucagon analogs were tested in a chemical stability assay in 50 mM phosphate buffer and the percentage of original concentration retained was determined after two weeks of incubation at 37° C.