Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.

The peptide hormone ghrelin is the endogenous ligand for the type 1a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant. GHS-R1a antagonism has therefore been proposed as a potential approach for obesity treatment. More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment.

A High-throughput two-phase partition assay to measure the activity of lipid-metabolizing enzymes.

A new method to measure the activity of lipid-metabolizing enzymes is described. Subsequent to an enzymatic reaction, a two-phase system (organic/aqueous) is established by the addition of a phase partition scintillation fluid (PPSF). The PPSF serves as a scintillation fluid, a phase partition agent, and a carrier/separator of an organic-soluble radiolabeled reaction substrate or product.

HTS in the new millennium: the role of pharmacology and flexibility.

Over the past decade, high throughput screening (HTS) has become the focal point for discovery programs within the pharmaceutical industry. The role of this discipline has been and remains the rapid and efficient identification of lead chemical matter within chemical libraries for therapeutics development. Recent advances in molecular and computational biology, i.

Okadaic acid increases glucose uptake in 3T3-L1 adipocytes by stimulating glucose transporter 1 expression.

We present evidence that chronic 24 hour treatment of 3T3-L1 adipocytes with the phosphatase inhibitor okadaic acid increases deoxyglucose uptake 25 fold with a maximal effect at a concentration of 35nM. This pharmacological response is associated with a 21 fold increase in expression of glucose transporter 1 (glut 1) mRNA. These findings are discussed with respect to glucose transporter gene regulation and insulin signalling and are compared to previous observations describing the acute effects of okadaic acid on glucose transporter translocation.

Specific antigen binding by proteins secreted by an antigen-specific T cell hybrid.

Antigen-specific molecules secreted by a murine T cell hybrid specific for azobenzene arsonate (ABA) were purified from ascites fluid by ion exchange chromatography and affinity for antigen. The antigen-specific proteins were purified 250 fold and were resolved predominantly as Mr 110,000 polypeptides by reduction and SDS-polyacrylamide gel electrophoresis. The ability of these molecules to bind antigen was analyzed by an ELISA using antigen-coated microtiter trays.