Endocrinology/Hormones

<p>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.</p>

<p>ANP (7-20) 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.</p>

<p>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.</p>

<p>This is an incretin hormone that causes glucose dependent release of insulin by pancreatic beta cells. It is the cleavage product of GLP-1 (1-36) amide peptide.  This peptide, human GLP-1 (7–36), shares the same sequence with preproglucagon (78-107), amide, human.</p>

<p>Residues 1-12 of the gastrointestinal hormone motilin, secreted from endocrine cells in the small intestines, mainly from the jejunum and duodenum, in response to the fasting, drinking water or the mechanical stimulus of eating.</p>

<p>PTH 1-34, is a biologically active peptide fragment of parathyroid hormone (PTH). PHT 1-34 has been shown to enhance bone fracture healing by promoting osteogenesis. PTH 1-34 also has chondrogenic properties.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.</p>

<p>C- terminal fragment of adrenocorticotropic hormone (ACTH) also known as corticotropin, and competitive antagonist of ACTH receptor (ACTHR), also known as melanocortin type 2 receptor (MC2R).ACTH is a member of the melanocortins-peptide family, this tropic hormone is produced and secreted by the anterior pituitary gland. ACTH is an important component of the hypothalamic-pituitary-adrenal (HPA) axis and is often produced in response to biological stress. ACTH acts to increase the production and release of cortisol via its interaction with ACTHR. Receptor activation increases the intracellular concentration of cAMP via adenylyl cyclase. Abnormal ACTH levels in the body have been linked to primary adrenal insufficiency/Addison's disease, Cushing's disease and secondary adrenal insufficiency.</p>

<p>ANP (1-23) 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 cardiovascular remodelling.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 pro-ANP (1-126) which is converted into the circulating forms by the type II transmembrane serine protease Corin.</p>

<p>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.</p>

<p>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.</p>

<p>A Chemerin-9 peptide derived from chemerin, a protein that is involved in a variety of functions such as autocrine, angiogenic, reproductive and chemotactic processes. Chemerin-9 binds to the chemerin receptor 23 (G-protein coupled receptor) and causes the receptors internalisation.</p>

<p>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.</p>

<p>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.</p>

<p>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.</p>

<p>ANP (13-26) 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.</p>

<p>This is a truncated exendin-4 peptide, the original peptide was 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 β-cells leading to regeneration of the pancreas. It is a ligand to the exendin receptor and increases pancreatic acinar cell 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.</p>

<p>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).</p>

<p>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.</p>

<p>Fulvestrant-d3 is a isotope labeled compound of Fulvestrant.an estrogen receptor (ER) antagonist and GPR30 agonist thatinduces apoptosis and autophagy.</p>

<p>Estrone-d4 3-Sulfate Sodium Salt is a deuterated compound of Estrone 3-Sulfate Sodium Salt. Estrone 3-Sulfate Sodium Salt has a CAS number of 438-67-5.</p>

<p>Estrone-d2 is a deuterated compound of Estrone. Estrone has a CAS number of 53-16-7. Estrone is an aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from ANDROSTENEDIONE directly, or from TESTOSTERONE via ESTRADIOL. In humans, it is produced primarily by the cyclic ovaries, PLACENTA, and the ADIPOSE TISSUE of men and postmenopausal women.</p>

<p>Lisinopril, an ACE inhibitor, treats hypertension, heart failure, heart attacks, and prevents diabetes-related eye and kidney issues.</p>

<p>A 274 is a highly aromatic, monosubstituted phenol antioxidant generated during differentiation of neuroblastoma cells.</p>

<p>L-6424 is an intermediate of Amiodarone and a non-selective ion channel blocker. It has an antiarrhythmic.</p>

<p>T3-ATA S-isomer, the S-isomer of T3-ATA, represents the active form of the thyroid hormone.</p>

<p>Fenclofenac: a non-steroidal anti-inflammatory that blocks T4 and T3 binding to TBG.</p>

<p>AR antagonist 6 (compound 6i), a diphenyl ether androgen receptor (AR) antagonist, binds to the AR with an affinity of 120 nM. It demonstrates low toxicity and effective in vitro activity in the golden Syrian hamster ear model. [19] [1]</p>

<p>GDC-2992 is a selective androgen receptor (AR) degradator that degrades AR and inhibits proliferation in VCaP cells,CRPC.</p>

<p>GRT2932Q is a nonpeptidic agonist of the opioid receptor-like 1 (ORL1) [1].</p>

<p>CGP-53153 is a steroidal inhibitor of 5 alpha-reductase (IC50s: 36 and 262 nM in rat and human prostatic tissue).</p>

<p>Estromustine, an active metabolite of estramustine phosphate, is used to treat prostate cancer.</p>

<p>ASN04885796 is a neuroprotective, specific GPR17 agonist with an EC50=2.27 nM for GPR17-mediated GTPγS binding and study neurodegenerative diseases</p>

<p>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.</p>

<p>Irbesartan-d4 (Irbesartan D4), a deuterated compound of Irbesartan, is an angiotensin receptor blocker and is used in the study of cardiovascular disease.</p>

<p>Losartan D4: deuterium-enriched Losartan, an angiotensin II blocker, with a 20 nM IC50.</p>

<p>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.</p>

<p>Procymidone is a broad-spectrum fungicide that inhibits fungal glycerol triester synthesis, thereby disrupting hyphal growth. androgen receptor (AR) antagonist</p>

<p>4-Hydroxytoremifene is a selective estrogen receptor modulator toremifene active metabolite.</p>

<p>Timobesone is a topical corticosteroid.</p>

<p>4'-Raloxifene-β-D-glucopyranoside is a metabolite of Raloxifene.</p>

<p>JNJ-37654032: orally active, nonsteroidal SARM. Mixed AR agonist/antagonist. Selective for muscle, grows levator ani, max at 3mg/kg, ED(50) 0.8mg/kg.</p>

<p>Endoxifen E-isomer hydrochloride (E-Endoxifen hydrochloride) , a tamoxifen metabolite, is effective specific Estrogen Response Modifier (SERM).</p>

<p>Diisopropyl phthalate is widely used as an additive in plastics and consumer products in the chemical industries.</p>

<p>Cilazapril Monohydrate (Justor) is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and congestive heart failure.</p>

<p>VTP-27999 is an alkyl amine Renin inhibitor. VTP-27999 has been used in trials studying the basic science of Renal Function.</p>

<p>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.</p>

<p>D-Kynurenine, ZINC901103, metabolizes from D-tryptophan, activates AhR, changes epithelium to mesenchyme, and tests for D-amino acid oxidase.</p>

<p>Lipidated Oxytocin analog with long-lasting activities. Product has the following disulfide bonds: Cys1-Cys6 and is available as a 0.5mg vial.</p>

<p>Fluticasone furoate (Avamys), a potent, trifluorinated steroid with anti-inflammatory effects, treats allergic rhinitis.</p>

<p>Liraglutide is sold under the brand name €˜Victoza' and is a medication used to treat diabetes mellitus type 2 and obesity.Liraglutide binds to and activates the GLP-1 (glucagon-like peptide-1) receptor to bring about an increase in insulin secretion and a decrease in glucagon secretion and gastric emptying.</p>

<p>Flumethasone pivalate: antipruritic, anti-inflammatory, and vasoconstrictor; for adrenocortical suppression, skin atrophy, and telangiectasia studies.</p>

Palosuran (ACT-058362) (ACT-058362) is a new potent and specific antagonist of the human UT receptor.

<p>Pomisartan (BIBR-363) is a small molecule angiotensin type 1 receptor (AT1R) antagonist that is used in the treatment of cardiovascular disease, studying heart</p>

<p>JHU-083 is a glutaminase antagonist that improves cognition and normalizes aberrant hippocampal glutaminase activity in APOE4 mice.</p>

AL 4114 is used as an aldose reductase inhibitor.

<p>Dexamethasone Beloxil is a glucocorticoid, Anti-inflammatory Agent.</p>

<p>Compound 30a, known as AR Antagonist 5, is a selective androgen receptor (AR) antagonist that demonstrates an IC 50 value of 134.8 nM. It exhibits favorable pharmacokinetic properties, characterized by high skin exposure and low plasma exposure [1].</p>

<p>Azetirelin, as a TRH analog, has a more potent effect than TRH on the central nervous system.</p>

<p>GPR120 modulator 2 is useful for modulating GPR120.</p>

<p>CGP48369 is a potent angiotensin II receptor antagonist with antihypertensive effects that enhances endothelium-dependent relaxation of coronary arteries in</p>

<p>FFA3 Agonist 1, a potent agonist of the free fatty acid receptor 3 (FFA3), plays a crucial role in mediating the health-promoting effects of the intestinal</p>

<p>MCHR1 antagonist 1 is a selective antagonist of melanin-concentrating hormone-1 (MCH1) receptor (Kb: 1 nM, Ki: 4 nM at human MCH1).</p>

<p>Topterone (Win 17,665) is a potent topical antiandrogen that inhibits the stimulation of lumbar organ development by testosterone and dihydrotestosterone in</p>

<p>SN34037, specific Aldo-keto reductase 1C3 (AKR1C3) inhibitor, inhibiting the cytotoxic activity of PR-104A, suitable for studying PR-104A-responsive leukaemia.</p>

<p>Bisphenol Z is a bisphenol compound and high-performance monomer used in advanced engineering plastics, having antagonistic activity towards ERα.</p>

<p>Ar-V7-IN-1 (compound 47) is a potent inhibitor of Ar-V7,associated with resistance to AR-targeted therapy with desmoplasia-resistant prostate cancer (mCRPC).</p>

<p>J 628 is a synthetic "impeded" estrogen derivative. It also has some postcoital antifertility activity.</p>

<p>KAT681 is a liver selective thyromimetic.</p>

<p>INCB13739 is an 11β-HSD1 inhibitor that can be used in the study of hyperlipidemia and hypertriglyceridemia.</p>

<p>Bifluranol (BX341) has anti-androgenic activity and has shown significant anti-prostatic activity in in vivo studies for the treatment of benign prostatic</p>

<p>S-40503 is an investigational selective androgen receptor modulator (SARM).</p>

<p>Cyproterone, an anti-androgen, treats female hirsutism and acne, and is used palliatively in prostate cancer.</p>

<p>CFMB is the FFA2 receptor agonist.</p>

<p>Bopindolol is a non-selective β-adrenergic receptor antagonist.</p>

<p>BW373U86 (SNC86), a δ-opioid receptor agonist, demonstrates potent activity with an IC50 value of 1.49 nM and has shown to exhibit antidepressant-like effects [</p>

<p>NGD-4715 is a selective and orally active antagonist of melanin-concentrating hormone receptor 1.</p>

<p>Oral GPR40 agonist 5 (EC50: 47 nM) lowers blood glucose and enhances tolerance, manages type 2 diabetes in mice.</p>

<p>RU 25055 is a synthetic antiglucocorticoid.</p>

<p>Ralaniten (EPI-002), a potent AR-NTD antagonist, inhibits AR with IC50 of 7.4 μM, for CRPC study.</p>

<p>Fludrocortisone （Florinef） is a synthetic corticosteroid with moderate glucocorticoid potency and greater mineralocorticoid potency.Cost-effective and quality-assured.</p>

<p>ALB-127158(a): Potent MCH1 receptor antagonist, potential IBD treatment.</p>

<p>AZD3514 is a potent and oral androgen receptor downregulator with Ki of 2.2 μM and has ability of reducing AR protein expression.Phase 1.</p>

<p>AR antagonist 2 (compound 58) is a potent inhibitor of the androgen receptor (AR) (IC50: 0.95 μM).</p>

<p>Tranilast Sodium has been used for the treatment of bronchial asthma. Tranilast is also used to autoimmune diseases, atopic and fibrotic pat.</p>

<p>SQ 30774 is a representative of the imidazole alcohols-a novel class of renin inhibitors.</p>

GPR40 Activator 1 is a potent GPR40 activator for treatment of type 2 diabetes.

<p>AS-1669058 free base is a G-protein-coupled receptor 119 (GPR119) agonist used to as new drug to treat type 2 diabetes.</p>

<p>AMG-076 is an antagonist of melanin-concentrating hormone receptor 1. It also reduced hERG inhibition.</p>

<p>Acolbifene hydrochloride binds to estrogen receptors in the body. It is a type of selective estrogen receptor modulator</p>

<p>DS20362725 is a selective estrogen-related receptor alpha (ERRα) agonist, commonly used in the study of metabolic disorders.</p>

<p>Cholesterol-d6 is a deuterated chlosterol that can be used to study lipid membrane flow and chlosterol metabolism in vivo.</p>

<p>VPC-14449 is a selective androgen receptor DNA-binding domain (AR-DBD) inhibitor, useful in prostate cancer research.</p>

<p>nor-Binaltorphimine dihydrochloride is a long-acting potent and highly selective kappa opioid receptor antagonist.</p>

<p>LY 43578 is an orally active aromatase inhibitor.</p>

<p>Estrogen receptor α antagonist 1 (compound 35) is a highly selective estrogen receptor α antagonist that acts on estrogen receptor α (IC50: 0.02 μM), estrogen</p>

<p>Embusartan (BAY 10-6734) is a potent, orally active angiotensin II receptor antagonist used as an antihypertensive agent.</p>

<p>Potent, selective oral GPR84 antagonist with IC50 of 8.95 nM, inhibits neutrophil/macrophage chemotaxis, potential in ulcerative colitis research.</p>

<p>Demegestone: synthetic progestogen, progesterone receptor agonist, treats luteal insufficiency, no androgenic activity.</p>

<p>L-751788 is an inhibits of type 1 5alpha-reductase.</p>

<p>σ 1 Receptor/ μ Opioid receiver modulator 1 (Compound 44) is an effective σ 1 receptor antagonist (Ki=1.86 nM) and μ Opioid receptor agonists (Ki=2.1 nM).</p>