Endocrinology/Hormones

NCRW0005-F05 is a potent agonist of orphan G-protein coupled receptor GPR139 with an IC 50 value of 0.21 μM.

Ethaselen (BBSKE) is an oral TrxR inhibitor with IC50 of 0.5 μM (human) and 0.35 μM (rat), targeting a selenocysteine site to fight NSCLC.

Originally identified in Heloderma horridum horridum (Mexican beaded lizard), exendin-3 shares homology with vasoactive intestinal peptide (VIP), secretin, helospectin I and II and helodermin. Exendin-3 increases cellular cAMP levels and amylase release from pig pancreatic cells.Truncated exendin-3 is a potent and selective GLP-1 receptor antagonist. It inhibits cAMP production and insulin release induced by GLP-1, exendin-3, and exendin-4. It also blocks the inhibitory effect of GLP-1 on food intake in rats. Exendin 3 (9-39) amide is being considered for clinical use in obese patients. This is based on the extensive and consistent data demonstrating its effectiveness as a tool to improve fasting and postprandial levels of glucose and glucagon.

Gastric inhibitory polypeptide (GIP) is an inhibiting hormone of the secretin family of hormones. While GIP is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion - in a glucose-dependent mechanism. Therefore, GIP is referred to as a glucose-dependent insulinotropic peptide. In GIP (Pro 3) the glutamic acid at position 3 has been substituted for a proline.GIP is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesised by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. GIP receptors are seven-transmembrane proteins found on β-cells in the pancreas. These β-cells are those that are able to simultaneously detect glucose and release insulin as a result to GIP binding.The clinical relevance of GIP is related to type 2 diabetes mellitus (T2DM)- studies have found that T2DM diabetics are unresponsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.

N-terminal tryptic peptide of parathyroid hormone (PTH), used for quantification and optimisation in LC-MS/MS assays.PTH is an 84-amino-acid polypeptide hormone (PTH 1-84) which is secreted by the parathyroid glands along with its fragments (such as PTH 1-34 and PTH 7-84). PTH increases calcium and decrease phosphate levels in the blood and the abundance of PTH-derived peptides is regulated by blood calcium levels. PTH inhibits the bone growth-promoting activity of osteoblasts and induces osteoclasts to resorb bone and release calcium and phosphate ions into the blood. PTH binds to and activates the receptor parathyroid hormone receptor 1 (PTHR1). PTHR1 is a G-protein-coupled receptor (GPCR) which regulates mineral ion homeostasis, bone turnover and skeletal development

This 32 amino acid peptide contains a 17 amino acid ring structure that is common to all natriuretic peptides. It is also called the brain natriuretic peptide (BNP) because it was first identified in porcine brain- however, the main source of this peptide is not the brain but the cardiac ventricle. This cardiac neurohormone is secreted from the ventricles in response to volume expansion and pressure overload. It has natriuretic and vasodilatory effects and suppresses the renin-angiotensin-aldosterone system.

Originally identified in Gila monster lizard (Heloderma suspectum), exendin-4 is an incretin mimetic, an analog of glucagon-like-peptide-1 (GLP-1), it stimulates insulin secretion and modulates gastric emptying to slow the entry of ingested sugars into the bloodstream. Exendin-4 is resistant to cleavage by plasma DPP-IV unlike GLP-1. This gives it a longer half-life and duration of action than GLP-1, as well as greater potency in vivo. Exendin-4 increases insulin sensitivity and improves glucose tolerance and is currently used for the treatment of Type 2 diabetes mellitus in its synthetic form Exenatide. Exendin-4 also promotes the production and proliferation of beta-cells leading to regeneration of the pancreas. It is a ligand to the exendin receptor and increases pancreatic acinni cAMP levels. However, the GLP-1 analog was found to have a toxic effect by inducing hypotension due to relaxation of the cardiac smooth muscle.

3,3',5-Triiodothyronine-(tyrosine ring-13C6) is the 13C labeled compound of 3,3',5-Triiodothyronine. 3,3',5-Triiodothyronine has a CAS number of 5817-39-0.

Originally identified in Heloderma horridum horridum (Mexican beaded lizard), exendin-3 is in the glucagon family. Exendin 3 stimulates vasoactive intestinal peptide (VIP) receptors in high concentrations. This leads to increased cAMP levels and amylase secretion in the pancreas. However, low exendin-3 exposure only increases cAMP levels. In applications, exendin-3 was found to induce hypotension by relaxation of cardiac, smooth muscle. Using a tag, exendin-3 is being investigated as a stable agonist for GLP1R to detect insulinomas, a pancreatic B cell-derived cancer with high GLP1R expression. Exendin 3 has also been used on mouse models to assess its effect on glucose-stimulated insulin secretion in glucagon receptor knockout (Gcgr-/-) backgrounds. Understanding the interplay between exendin 3 and metabolism could provide new insights into the obesity crisis.