Endocrinology/Hormones

ER degrader 10 (Compound 51) is an orally active estrogen receptor (ER) selective degrader and antagonist, with a DC50 of 0.43 nM and an IC50 of 0.56 nM. It inhibits the proliferation of ER-positive cells, with an IC50 ranging from 0 to 15 nM. ER degrader 10 exhibits weak inhibitory activity on the hERG channel, with an IC50 greater than 40 μM. It has blood-brain barrier permeability, with a brain/plasma ratio (Kp) of 3.05. In mouse models, ER degrader 10 demonstrates antitumor activity.

Relacorilant is an oral glucocorticoid receptor antagonist with Ki of 7.2 nM, potential for treating Cushing's syndrome.

This assay employs the competitive inhibition enzyme immunoassay technique. The microtiter plate provided in this kit has been pre-coated with Mouse MDA protein. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Mouse MDA. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Mouse MDA in the samples is then determined by comparing the OD of the samples to the standard curve.

The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Rat VLDL. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Rat VLDL. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Rat VLDL, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Rat VLDL in the samples is then determined by comparing the OD of the samples to the standard curve.

The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Horse IGF1. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Horse IGF1. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Horse IGF1, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Horse IGF1 in the samples is then determined by comparing the OD of the samples to the standard curve.

Cebranopadol (GRT6005) is an analgesic NOP and opioid receptor agonist with Kis of 0.9 nM, 0.7 nM, 2.6 nM, 18 nM for human NOP, μ-opioid (MOP), κ-opioid (KOP)

Pamoic acid is the orphan G protein-coupled receptor GPR35 agonist. Pamoic acid activates ERK and beta-arrestin2 and causes antinociceptive activity.

SR17018 is an mu-opioid-receptor (MOR) agonist, binding with GTPγS, with an EC50 of 97 nM.

The cleavage of proglucagon forms glucagon. Increased levels of glucagon that can't be regulated are linked to diabetic hyperglycaemia and other pathologies. Typically, glucagon levels should be suppressed as glucose levels rise. However, the opposite has generally been found to be accurate, and the nature of this elevated immunoreactive glucagon has led to more research. Hyperglucagonaemia is a characteristic of several pathologies, but the detection of immunoreactive glucagon has yet to be fully verified due to the nature of available detection.Glucagon can be hydrolysed by dipeptidyl peptidase IV (DPIV) to products such as (18-29) and (3-29). Current methods for detecting glucagon rely on antibodies to the N terminus or  C-terminus to detect pancreatic glucagon. However, these antibodies may also detect truncated forms due to a pathology affecting the secretion, clearance or processing of proglucagon-derived peptides. Theoretically, these can be used in a sandwich process to detect only full-length glucagon. Therefore, the availability of the truncated glucagon (3-29) as a control to test the sensitivity of the available antibodies and the ELISAs is useful. Plasma levels from hyperglucagonaemic patients and healthy counterparts were used as a control to test the commercial glucagon assays and ELISAs. The truncated glucagon (3-29) provided valuable information about the sensitivity and specificity of the antibodies that have been used as an industry standard for glucagon measurement. This truncated glucagon is vital in ensuring our research moves forward with more controls and fewer assumptions.

Mammalian bombesin-like neuropeptide- first isolated from pig spinal cord, which can stimulate rat uterine smooth muscle contraction and gastrin and somatostatin secretion in vitro. Increases blood pressure and pancreatic exocrine secretion in dogs.

Peptide derived from the Gastric inhibitory polypeptide (GIP), 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.GIP is derived from a 153-amino acid pro-protein 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.

The heptapeptide Alexamorelin is a member of the Growth Hormone secretagogues (GHS) family. These are synthetic molecules which act through the central nervous system to stimulate the secretion of somatotrophs, prolactin, adrenocorticotrophin and cortisol. Alexamorelin has also been shown to inhibit 125I-Tyr-Ala-HEX binding in tissues. Due to their stimulation of growth hormone release, they are known as non-approved pharmaceuticals and are a concern to sport's drug testing organisations.

Mammalian bombesin-like peptide neurotransmitter that is an agonist for the gastrin-releasing peptide receptor (GRPR). It exhibits physiological functions such as gastrin and somatostatin release and chemoattraction within the immune system.

Insulin is a polypeptide composed of two peptide chains referred to as the alpha chain and β chain. These chains are linked by two disulphide bonds, and an additional disulphide is formed within the alpha chain. In most species, the alpha chain consists of 21 amino acids and the β chain of 30 amino acids. Insulin is normally secreted rapidly from the β-cells of the pancreatic islets in response to nutrients absorbed after a meal. In type 1 diabetes mellitus, there may be an absolute insulin deficiency as a consequence of autoimmune destruction of the β-cells. On the other hand, in type 2 diabetes mellitus, insulin secretion is impaired and is inadequate to overcome peripheral insulin resistance.

Natural cleavage product of GLP-1 which, unlike GLP-1, does not affect either insulin secretion or glucose homeostasis.  GLP-1(9-36) has low affinity for, and acts as an antagonist to, the GLP-1 receptor.GLP-1 (9-36) does however display unique biological activities such as beneficial cardiovascular effects and reducing the production of reactive oxygen species (ROS). GLP-1 (9-36) also exerts important physiological effects on neuronal plasticity in the hippocampus, and inhibits chemokine-induced migration of human CD4-positive lymphocytes.GLP-1 (9-36) is formed from the breakdown of biologically active but highly unstable GLP-1 (7-36) amide by the ubiquitous serine protease, dipeptidyl peptidase-IV (DPP-IV).

ANP (9-22) is derived from the atrial natriuretic peptide (ANP) which is a cardiac hormone involved in maintaining cardio-renal homeostasis. This occurs through the activation of the guanylyl cyclase-coupled receptor, resulting in the increased concentration of cyclic guanylate monophosphate. Moreover its function in the processes of anti-proliferation and anti-angiogenesis allow it to take part in the cardiovascular remodelling process.ANP is a member of the natriuretic peptide family and it is encoded by the NPPA gene, located on chromosome 1. Once synthesized from the 151 amino acid pre-prohormone into its biologically active form, ANP is secreted by the atrial cardiomyocytes in the circulating forms: ANP (1-98) and ANP (99-126). This synthesis process involves the signal peptide being removed from the pre-prohormone resulting in proANP (1-126) which is converted into the circulating forms by the type II transmembrane serine protease Corin.

The hormone Calcitonin, reduces the amount of serum calcium during hypercalcemia and is released from the C-cells of the thyroid gland. Within its structure it contains a disulphide bridge between cysteine 1 and 7 and a proline at its carboxy terminal.Calcitonin is used therapeutically in the treatment of hypercalcemia diseases such as Paget disease, Sudeck atrophy, bone metastases and vitamin-D intoxication.The level of calcitonin in the plasma can also be used as a marker for medullary thyroid carcinoma, while procalcitonin is used to diagnose sepsis.

Glucagon like-peptide-2 (GLP-2) is a gut hormone produced in the enteroendocrine L cells of gastrointestinal tract by the cleavage of the 160-amino-acid proglucagon molecule. GLP-2 is secreted following the ingestion of food and carries out its activities via the GLP-2 G-protein coupled receptors (GLP-2Rs). GLP-2 has a range of roles within the cell, including: anti-inflammatory effects promoting the expansion of the intestinal mucosa, stimulating intestinal blood flow, inhibiting gastric acid secretion and gastric emptying, increasing intestinal barrier function and enhancing nutrient and fluid absorption.

Estrogen Receptor Modulator 8 (compound 4) is an orally active inhibitor targeting Estrogen Receptor/ERR α with potent efficacy (IC50 = 0.437 nM in MCF-7 cells

MOR Agonist-1 is a μ-opioid receptor (MOR) agonist noted for its potent analgesic properties and is utilized in research concerning pain and associated