• Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). (drugbank.com)
  • Within the last three years two alternative anti-androgen strategies reached clinical application offering new options in both pre- and post-chemotherapy setting which emphasises the androgen receptor as sustained therapy target in prostate cancer. (springeropen.com)
  • 2012 ). Even for the second-generation anti-androgen enzalutamide a ligand binding domain mutation has been identified which converts the drug from an AR antagonist to an AR agonist. (springeropen.com)
  • The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone slow the course of DKD as well as the risk of hospitalizations and death in patients with heart failure (HF) with reduced ejection fraction but their potential of causing hyperkalemia, particularly in individuals with renal dysfunction, restricts their usage. (gjmpbu.org)
  • Finerenone, a new non-steroidal MRA, has showed potential cardiac and renoprotective advantages in DKD as well as has a better affinity for the mineralocorticoid receptor (MR) than eplerenone and higher selectivity for the MR than spironolactone. (gjmpbu.org)
  • The mechanism of action of spironolactone involves its ability to bind to the mineralocorticoid receptor in the kidneys. (greenspooncafe.com)
  • Complex interaction involving opposition of hypokalemia by drug at mineralocorticoid receptor, and possible reduction in licorice adverse effect of hypertension. (interactionsguide.com)
  • Both darolutamide and ketodarolutamide show limited central nervous system distribution, indicating peripheral selectivity, and little or no inhibition or induction of cytochrome P450 enzymes such as CYP3A4, unlike enzalutamide and apalutamide. (wikipedia.org)
  • Several adverse outcome pathways (AOPs) have linked molecular initiating events like aromatase inhibition, androgen receptor (AR) agonism, and estrogen receptor (ER) antagonism to reproductive impairment in adult fish. (bvsalud.org)
  • The first AOP (346) documents events starting with inhibition of cytochrome P450 aromatase (CYP19), resulting in decreased availability of 17ß-estradiol during gonad differentiation, which increases the occurrence of testis formation, resulting in a male-biased sex ratio and consequent population-level declines. (bvsalud.org)
  • This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis. (drugbank.com)
  • These data and in vitro metabolism data suggest that, upon multiple dosing, metabolic enzyme inhibition may occur for this drug. (guidelinecentral.com)
  • The mode of action of these new compounds is either inhibition of androgen synthesis at the CYP17A1 enzyme covering also adrenal and intracrine androgen sources, or a full androgen receptor (AR) blockade antagonizes the AR function by directly binding this transcription factor with high affinity. (springeropen.com)
  • 19. Reliable Prediction of Human Cytochrome P450 Inhibition Using Artificial Intelligence Approaches, Journal of Chemical Information and Modeling , 2019, 59, 4587-4601. (zju.edu.cn)
  • Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. (researchgate.net)
  • Nilutamide through its antiandrogenic activity can complement surgical castration, which suppresses only testicular androgens. (guidelinecentral.com)
  • By binding to this receptor, spironolactone blocks the effects of aldosterone, a hormone that promotes the reabsorption of sodium and the excretion of potassium in the kidneys. (greenspooncafe.com)
  • Overall, spironolactone helps to lower blood pressure, reduce fluid retention, and counteract the effects of excess androgens in certain conditions. (greenspooncafe.com)
  • Aromatase is a crucial enzyme for the biosynthesis of estrogens and is involved in the process of breast carcinogenesis. (spandidos-publications.com)
  • The effects of zeranol on cell proliferation were measured using the MTS assay, aromatase expression levels were determined by immunocytochemical staining and reverse transcription‑polymerase chain reaction, and aromatase enzyme activity and estrogen production were analyzed using corresponding assay kits. (spandidos-publications.com)
  • The synthesis of estrogens in breast tissue is catalyzed by the enzyme aromatase, which is encoded by the gene cytochrome P450 family 19 subfamily A member 1 (CYP19A1). (spandidos-publications.com)
  • Aromatase is a cytochrome P450, which synthesizes estrogens by converting C19 androgens to aromatic C18 estrogenic steroids, thus catalyzing the rate-limiting or final step of estrogen synthesis ( 5 , 6 ). (spandidos-publications.com)
  • Aromatase inhibitors are considered to be a standard of therapy and drug class of choice for the treatment of early breast cancer in postmenopausal women with hormone-receptor positive disease. (empowerpharmacy.com)
  • The American Society of Clinical Oncology recommends that all postmenopausal women with hormone receptor-positive early breast cancer receive adjuvant aromatase inhibitor therapy. (empowerpharmacy.com)
  • Anastrozole inhibits aromatase, the enzyme that catalyzes the final step in estrogen production. (empowerpharmacy.com)
  • Anastrozole is an oral, competitive, non-steroidal inhibitor of aromatase and is less likely to exhibit agonist or antagonist steroidal properties. (empowerpharmacy.com)
  • Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. (absoluteastronomy.com)
  • In vitro, nilutamide blocks the effects of testosterone at the androgen receptor level. (guidelinecentral.com)
  • GnRH agonists bind to the GnRH receptors on pituitary gonadotropin-producing cells, causing an initial release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and consequently a rise in testosterone levels for a few weeks. (medscape.com)
  • Antiandrogens bind to androgen receptors and competitively inhibit their interaction with testosterone and dihydrotestosterone. (medscape.com)
  • Stereoselectivity and the potential endocrine disrupting activity of di-(2-ethylhexyl)phthalate (DEHP) against human progesterone receptor: a computational perspective. (endometriosi.it)
  • Binding of DEHP to progesterone receptor (PR) represents a potential mechanism of interference in the reproductive functions. (endometriosi.it)
  • Prof. Cruciani is the scientific director of Molecular Discovery company based in London, and is the scientific director of the human Cytochrome Consortium Initiative (a consortium of seven pharmaceutical companies collaborating to address metabolism issues in predictive human metabolism). (ldorganisation.com)
  • 4 These chemicals can affect the endocrine and reproductive systems in 4 major ways: by mimicking or antagonizing the effect of endogenous hormones and by disrupting the synthesis and metabolism of endogenous hormones or their receptors. (ndnr.com)
  • Per the manufacturer, it is unlikely that anastrozole administered at the recommended dose will inhibit the metabolism of cytochrome P450-mediated drugs given concomitantly. (empowerpharmacy.com)
  • this is an exogenous agent that interferes in the production, liberation, transport, metabolism, the union to a receptor or a modifier of the action or elimination of natural ligands responsible for maintaining homeostasis and the regulation and development of the organism. (ivis.org)
  • Not only does DIM work directly on estrogen metabolism and receptor activity, but it also works to stimulate cellular detoxification pathways, which theoretically may indirectly help support the prevention of various cancers. (casi.org)
  • CYP enzymes also help regulate steroid hormone metabolism and are involved in converting estrogen metabolites to their safer forms. (casi.org)
  • Potassium-sparing diuretics, like aldosterone antagonists or potassium-sparing diuretics, work by blocking the action of aldosterone, a hormone that promotes potassium excretion. (greenspooncafe.com)
  • Discussion Gene-mediated enzyme replacement is a reasonable and decidedly promising approach adrawst the treatment of FD. (upb.ro)
  • 2002) CAG repeat burgeoning in the androgen receptor gene is not associated with male infertility in Indian inhabitantss. (upb.ro)
  • Second, DIM selectively modulates gene activity via its action on estrogen receptors. (casi.org)
  • Participants with de novo metastatic NE prostate cancer will not be required to have been previously treated with androgen deprivation therapy (ADT). (aiom.it)
  • Albendazole also has been shown to inhibit the enzyme fumarate reductase, which is helminth-specific. (parasitetesting.co.uk)
  • Estrogen receptor agonists can also cause adverse reproductive effects, however, the early key events (KEs) in an AOP leading to this are mostly unknown. (bvsalud.org)
  • Treatment with luteinizing hormone-releasing hormone agonists or antagonists for all cohorts must have been initiated ≥4 weeks prior to first dose of study therapy and must be continued throughout the study. (aiom.it)
  • Prostate cancer is known to be androgen sensitive and responds to androgen ablation. (guidelinecentral.com)
  • Our cancer studies have expanded to include oesophageal cancer with emphasis on oestrogen receptor expression and function in this malignancy. (nottingham.ac.uk)
  • Recent breakthrough therapies targeting androgen receptor signalling in castration resistant prostate cancer (CRPC) involve multifunctional androgen receptor (AR) blockade and exhaustive androgen deprivation. (springeropen.com)
  • Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. (drugbank.com)
  • In silico analyses by molecular docking to model ligand-protein interactions, and by SwissADME and ADMET webservers to establish the pharmacokinetic profile of the four investigated compounds in interaction with the angiogenesis target protein HIF-1α/breast cancer (PDB ID: 3KCX) and human androgen receptor/prostate cancer (PDB ID: 1E3G) were performed. (springeropen.com)
  • The activated estrogen receptor binds to specific DNA sequences or hormone-response elements, which enhances transcription of adjacent genes and, in turn, leads to the observed effects. (medscape.com)
  • AA treatments of AR positive CRPC cell models led to decreased expression of androgen regulated genes such as PSA. (springeropen.com)
  • In these cells diminished expression of androgen regulated genes was accompanied by an up-regulation of CYP17A1 expression within short-term treatments. (springeropen.com)
  • Down-regulation of androgen regulated genes occurs in spite of an elevated expression of CYP17A1, the very target enzyme for this drug. (springeropen.com)
  • Expression and estrogen sensitivity of target genes and nuclear receptor coregulators were altered at mRNA and protein levels in adult uterus, prostate and brain. (researchgate.net)
  • According to researchers, DIM may help modulate aryl hydrocarbon receptor (AhR) , which promotes transcription of genes that stimulate the expression of detoxification enzymes from the phase I cytochrome P450 (CYP) family. (casi.org)
  • Interestingly, while genes involved in immune system function were down-regulated in the brains of mature males, changes in the expression levels of several receptors and channels were observed suggesting that some rewiring is occurring in the brain at sexual maturity. (biomedcentral.com)
  • New drugs including abiraterone acetate (AA) and enzalutamide, effectively target the androgen pathway to arrest aberrant signalling even after multiple therapies. (springeropen.com)
  • Ligand 3 does not interact with the selected receptors via hydrogen bonds. (springeropen.com)
  • Nuclear receptor coactivators associate in a ligand-dependent manner with estrogen receptors (ER) and other nuclear receptors, and they enhance ligand-dependent transcriptional activation. (bioone.org)
  • Because endogenous chemicals bind and activate FXR, it is important to examine which xenobiotic compounds would disrupt normal receptor function. (nature.com)
  • Estrogens diffuse through cell membranes, distribute themselves throughout the cell, and bind to and activate the nuclear estrogen receptor, a DNA-binding protein found in estrogen-responsive tissues. (medscape.com)
  • Similarly to its parent compound, ketodarolutamide acts as a highly selective, high-affinity, competitive silent antagonist of the androgen receptor (AR). (wikipedia.org)
  • The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide. (drugbank.com)
  • The receptor 1E3G displayed poor binding affinity energy to all tested compounds with energy value above − 11.99 kcal/mol (co-crystal). (springeropen.com)
  • This study aimed to examine the interaction of four cytotoxic compounds isolated from Madagascar endemic medicinal plants Diospyros quercina and Salacia leptoclada with both angiogenesis target protein HIF-1α and human androgen receptor (HAR) by evaluating binding affinity energy of formed complex and defining the amino residues involved in such interaction. (springeropen.com)
  • New putative receptors for endocannabinoids, such as GPR55, have been recently identified, and there is a possibility that these receptors contribute to off-target endocannabinoid effects in order to suppress cancer cell viability [ 13 ]. (biomedcentral.com)
  • In vivo, nilutamide interacts with the androgen receptor and prevents the normal androgenic response. (guidelinecentral.com)
  • Approval for the adjuvant treatment of early breast cancer in postmenopausal women with hormone receptor positive disease was received in September 2002. (empowerpharmacy.com)
  • Antioxidant enzyme expression, lipid peroxidation, and protein oxidation in human myometrium with parturition Reproductive Sciences. (nottingham.ac.uk)
  • The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. (researchgate.net)
  • of G-protein coupled receptors. (researchgate.net)
  • The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (nih.gov)
  • Structure-activity relationships of FXR-active compounds revealed by this screening were then compared against the androgen receptor, estrogen receptor α, peroxisome proliferator-activated receptors δ and γ and the vitamin D receptor. (nature.com)
  • In particular we are studying the role of eicosanoids in normal pregnancy and preeclampsia, the contribution of a purinergic receptor to the release of the cytokine interleukin-1beta in pregnancy as well as investigation of the inflammasome in coordinating inflammatory pathways coupled to cytokine release. (nottingham.ac.uk)
  • This group of enzymes is important for regulating the body's inflammatory response pathways, acts as antioxidants, and enhances the excretion of genotoxins. (casi.org)
  • A direct effect on steroid receptor sites in breast tissue is also possible. (drugbank.com)
  • The development and progression of estrogen-driven cancers, including both breast and prostate cancers, usually involves the action of 17-beta-estradiol (E2) upon estrogen receptors including ERβ in the prostate epithelium. (casi.org)
  • The second AOP (376) is initiated by activation of the androgen receptor (AR), also during sexual differentiation, again resulting in a male-biased sex ratio and population-level effects. (bvsalud.org)
  • While conventional drugs such as the α1-adrenergic receptor antagonists and 5α-reductase inhibitors have been found to be useful in the treatment of BPH, the adverse side effects associated with their usage, have led to increased search for alternative means of managing this disease. (frontiersin.org)
  • These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. (biomedcentral.com)
  • Elevation of liver enzymes during treatment is a common side effect, but in rare cases there have also been reports of acute liver failure. (parasitetesting.co.uk)
  • Endocannabinoids are endogenously-produced cannabinoids that are involved in a variety of physiological processes (including pain-sensation and memory) through the activation of cannabinoid receptors [ 1 ]. (biomedcentral.com)
  • Evidence suggests that endocannabinoids might suppress cancer cell viability through the activation of classic cannabinoid receptors such as cannabinoid receptor-1/2 (CB1 and CB2) and vanilloid receptor-1 (VR1). (biomedcentral.com)
  • The purinergic P2X 7 receptor: regulation of uterine function in labour and preterm labour. (nottingham.ac.uk)