Small molecules play a pivotal role in Endocrinology Research. These are low molecular weight compounds that have a significant impact on the endocrine system, hormones, and their receptors. Here are some key aspects of how small molecules are involved in this field:
Hormone Mimetics and Inhibitors: Small molecules are used to develop synthetic compounds that mimic the actions of hormones or inhibit their effects. For example, drugs like metformin for diabetes management and selective estrogen receptor modulators (SERMs) for breast cancer treatment are used to either mimic or block hormonal activity.
Receptor Modulation: Small molecules can bind to hormone receptors and modulate their activity. This is crucial in developing drugs that target specific hormone receptors, like the use of small molecule agonists and antagonists to regulate thyroid hormone receptors.
Metabolism Regulation: Endocrinology research often focuses on metabolism and how hormones like insulin regulate it. Small molecules are employed to understand and develop drugs targeting enzymes involved in metabolism, such as glucagon-like peptide-1 (GLP-1) agonists for diabetes treatment.
Steroid Hormone Production: Small molecules may be utilized to influence the production of steroid hormones in the adrenal glands or gonads. This is essential for conditions like Cushing's syndrome or polycystic ovary syndrome (PCOS).
Hormone Assays: In laboratory research, small molecules are used as tracers or markers in hormone assays. For instance, small molecule fluorophores can be attached to antibodies to detect hormone levels in blood samples.
Drug Development: Endocrinology research relies on small molecules as potential drug candidates. Researchers design and test small molecules for their effectiveness in modulating hormonal pathways, with the goal of developing new therapies for endocrine disorders. In summary, small molecules are indispensable tools in Endocrinology Research, enabling scientists to better understand the endocrine system's intricacies and develop novel treatments for a wide range of hormonal disorders and conditions. Their versatility and specificity make them valuable assets in advancing our knowledge of endocrinology and improving patient care.
Bazedoxifene is a third generation selective estrogen receptor modulator (SERM). Bazedoxifene acetate significantly prevents bone mass loss at 20 mg/day in healthy postmenopausal women with normal or low bone mineral density.
Meclizine is a human pregnane X receptor (hPXR) agonist. It possesses anticholinergic, central nervous system depressant, and local anesthetic effects. Its antiemetic and antivertigo effects are not fully understood, but its central anticholinergic properties are partially responsible.
Ozarelix is a fourth generation GnRH antagonist, induces apoptosis in hormone refractory androgen receptor negative prostate cancer cells modulating expression and activity of death receptors.
MBX-2982 is a potential first-in-class treatment for type 2 diabetes that targets G protein-coupled receptor 119 (GPR119), a receptor that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion.
acolbifene is a substance being studied in the prevention of breast cancer in women at high risk of breast cancer. Acolbifene hydrochloride binds to estrogen receptors in the body and blocks the effects of estrogen in the breast. It is a type of selective estrogen receptor modulator (SERM).
BMS-564929 is a novel, highly potent, orally active, nonsteroidal tissue selective androgen receptor (AR) modulator, and this compound has been advanced to clinical trials for the treatment of age-related functional decline.
PD 123319 ditrifluoroacetate is a potent, selective, non-peptide angiotensin AT2 receptor antagonist. IC50 values are 34 and 210 nM in rat adrenal tissue and brain respectively.
Arzoxifene HCl is the hydrochloride salt of arzoxifene, a synthetic aromatic derivative with anti-estrogenic properties. Arzoxifene binds to estrogen receptors as a mixed estrogen agonist/antagonist.
Orteronel (TAK700) is an androgen synthesis inhibitor. It selectively inhibits the enzyme CYP17A which is expressed in testicular, adrenal, and prostatic tumor tissues.
Captopril Disulfide is a reversible and competitive inhibitor of LTA4 hydrolase (IC50=11 M). Captopril has been shown to be an of angiotensin converting enzyme-1 (ACE1), but not ACE2(IC50 = 22 nM).
IRL-2500 is a potent, selective ETBR antagonist. It shows some selectivity for ETB receptors (IC50 values are 1.3 and 94 nM for ETB and ETA receptors respectively).
AR-231453 is a potent and selective small molecule agonis of GPR119 that enhances glucose dependent insulin secretion and glucagon like peptide-1 (GLP-1) release.
Tanaproget is a novel nonsteroidal progesterone receptor agonist which can bind to the PR from various species with a higher relative affinity than reference steroidal progestins.
KB130015 is a novel activator of hERG1 potassium channels, blocking native and recombinant hERG1 channels at high voltages, but activating them at low voltages.
NIBR189 is a small molecule antagonist of the Epstein-Barr virus-induced gene 2 (EBI2; GPR183) receptor with IC50 of 16 nM(Binding) and 11 nM (Functional).
Brilanestrant (GDC-0810, ARN-810??? is a potent ER-α binder (ER-α, IC50 = 6.1 nM; ER-β, IC50 = 8.8 nM), a full transcriptional antagonist with no agonism and displays good potency and efficacy in ER-α degradation (EC50 = 0.7 nM) and MCF-7 breast cancer cell viability (IC50 = 2.5 nM) assays with good selectivity over other nuclear hormone receptors.
Esaxerenone, also known as CS-3150, XL-550, is a nonsteroidal antimineralocorticoid that acts as a highly selective silent antagonist of the mineralocorticoid receptor (MR), the receptor for aldosterone, with greater than 1,000-fold selectivity for this receptor over other steroid hormone receptors, and 4-fold and 76-fold higher affinity for the MR relative to the existing antimineralocorticoids spironolactone and eplerenone.
Exicorilant (CORT 125281) is a selective and oral active glucocorticoid receptor (GR) antagonist, with a Ki value of 7 nM. Exicorilant (CORT 125281) has potential to overcome adiposity, glucose intolerance and dyslipidaemia.
ML401 is an antagonist of the EBI2 receptor with an IC50 of 1.03 nM. ML401 displays activity in a chemotaxis assay (IC50=6.24 nM). ML401 shows good stability and no toxicity.
AZD2906 is a selective glucocorticoid receptor (GR) agonist, increases micronucleated immature erythrocytes in the bone marrow of rats. AZD2906 shows IC50s of 2.2, 0.3, 41.6 and 7.5 nM at GR in human, rat PBMC and human, rat whole blood, respectively.
Apararenone (MT-3995) is a novel non-steroidal mineralocorticoid receptor antagonists under development for the treatment of diabetic nephropathies and non-alcoholic steatohepatitis.
PF-06747711 is a potent, selective, and orally active retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) inverse agonist, with an IC50 of 4.1 nM. Anti-skin inflammatory activity.
