Adamantyl ethanone pyridyl derivatives: potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.

PubWeight™: 0.78‹?›

🔗 View Article (PMC 3179844)

Published in ChemMedChem on June 28, 2011

Authors

Xiangdong Su1, Fabienne Pradaux-Caggiano, Nigel Vicker, Mark P Thomas, Heather Halem, Michael D Culler, Barry V L Potter

Author Affiliations

1: Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath BA27AY, UK.

Articles cited by this

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev (2000) 15.16

Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation (2005) 8.54

A transgenic model of visceral obesity and the metabolic syndrome. Science (2001) 6.22

11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev (2004) 3.56

Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol (2004) 3.43

Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab (2003) 3.33

Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab Dispos (1999) 3.07

11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc Natl Acad Sci U S A (1997) 3.00

Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet (1987) 2.50

Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action. Endocrinology (2001) 2.21

Glucocorticoids and muscle catabolism. Curr Opin Clin Nutr Metab Care (1999) 2.16

11beta-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice. J Exp Med (2005) 2.12

Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes (2004) 2.12

Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. J Clin Invest (2003) 1.95

Selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice. Diabetologia (2002) 1.77

Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. Endocrinology (2003) 1.66

The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy. Diabetes Care (2010) 1.66

Cortisol effects on body mass, blood pressure, and cholesterol in the general population. Hypertension (1999) 1.58

Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing's disease during active disease and 1 year after disease remission. J Clin Endocrinol Metab (2003) 1.52

Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity. Diabetes (2005) 1.40

The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane. J Biol Chem (1999) 1.26

Cortisol--cause and cure for metabolic syndrome? Diabet Med (2006) 1.25

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 as a promising therapeutic target. Drug Discov Today (2007) 1.20

Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J Clin Endocrinol Metab (1995) 1.19

Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. J Clin Endocrinol Metab (2003) 1.19

Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab (2001) 1.14

11-Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors in type 2 diabetes mellitus and obesity. Expert Opin Investig Drugs (2008) 1.12

Glucocorticoids regulate the induction of phosphoenolpyruvate carboxykinase (GTP) gene transcription during diabetes. J Biol Chem (1993) 1.11

Blockade of glucocorticoid excess at the tissue level: inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 as a therapy for type 2 diabetes. J Med Chem (2008) 1.01

NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning and characterization of cDNA from sheep kidney. J Biol Chem (1994) 1.01

Pathophysiology of modulation of local glucocorticoid levels by 11beta-hydroxysteroid dehydrogenases. Trends Endocrinol Metab (2001) 1.00

11beta-hydroxysteroid dehydrogenase type 1 inhibitors as promising therapeutic drugs for diabetes: status and development. Curr Med Chem (2010) 0.98

Inhibition of 11beta-HSD1 as a novel treatment for the metabolic syndrome: do glucocorticoids play a role? Expert Rev Cardiovasc Ther (2005) 0.93

Modulation of 11beta-hydroxysteroid dehydrogenase (11betaHSD) activity biomarkers and pharmacokinetics of PF-00915275, a selective 11betaHSD1 inhibitor. J Clin Endocrinol Metab (2007) 0.92

Local amplification of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 and its role in the inflammatory response. Ann N Y Acad Sci (2006) 0.92

11beta-hydroxysteroid dehydrogenase type 1 inhibitors: a review of recent patents. Expert Opin Ther Pat (2009) 0.91

Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab (1995) 0.90

Discovery of adamantyl ethanone derivatives as potent 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors. ChemMedChem (2010) 0.86

Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery. Future Med Chem (2011) 0.85

Adamantane sulfone and sulfonamide 11-beta-HSD1 Inhibitors. Bioorg Med Chem Lett (2006) 0.83

Cortisol, Cushing's Syndrome, and a shrinking brain-new evidence for reversibility. J Clin Endocrinol Metab (2002) 0.83

Inhibitors of 11beta-hydroxysteroid dehydrogenase type 1. Prog Med Chem (2008) 0.82

11beta-hydroxysteroid dehydrogenase type 1 inhibitors for metabolic syndrome. Curr Opin Investig Drugs (2008) 0.79

Articles by these authors

Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques. Diabetes (2012) 1.91

Identification of mammalian Vps24p as an effector of phosphatidylinositol 3,5-bisphosphate-dependent endosome compartmentalization. J Biol Chem (2003) 1.76

Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase. Curr Biol (2002) 1.69

Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents. Chem Biol (2010) 1.66

Determination of neo- and D-chiro-inositol hexakisphosphate in soils by solution 31P NMR spectroscopy. Environ Sci Technol (2012) 1.53

Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab (2008) 1.45

Inhibition of the phosphatidylinositol 3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumor effects. Cancer Res (2005) 1.38

Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease. J Neurochem (2007) 1.35

Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors. J Med Chem (2010) 1.32

NAADP-mediated Ca2+ signaling via type 1 ryanodine receptor in T cells revealed by a synthetic NAADP antagonist. Proc Natl Acad Sci U S A (2009) 1.30

Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway. Oncogene (2004) 1.28

Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology (2007) 1.25

2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity. J Med Chem (2006) 1.25

Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinology (2007) 1.23

Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring) (2012) 1.19

Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. Peptides (2009) 1.16

Synthetic partial agonists reveal key steps in IP3 receptor activation. Nat Chem Biol (2009) 1.12

Inhibition of in vitro angiogenesis by 2-methoxy- and 2-ethyl-estrogen sulfamates. Int J Cancer (2004) 1.11

Phase I study of STX 64 (667 Coumate) in breast cancer patients: the first study of a steroid sulfatase inhibitor. Clin Cancer Res (2006) 1.10

Novel 18beta-glycyrrhetinic acid analogues as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenases. Bioorg Med Chem (2004) 1.10

Novel non-steroidal inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1. J Steroid Biochem Mol Biol (2007) 1.10

17beta-hydroxysteroid dehydrogenase Type 1, and not Type 12, is a target for endocrine therapy of hormone-dependent breast cancer. Int J Cancer (2008) 1.10

The role of 17beta-hydroxysteroid dehydrogenases in modulating the activity of 2-methoxyestradiol in breast cancer cells. Cancer Res (2006) 1.09

3,17-disubstituted 2-alkylestra-1,3,5(10)-trien-3-ol derivatives: synthesis, in vitro and in vivo anticancer activity. J Med Chem (2007) 1.04

Taspoglutide, an analog of human glucagon-like Peptide-1 with enhanced stability and in vivo potency. Endocrinology (2010) 1.04

STX140 is efficacious in vitro and in vivo in taxane-resistant breast carcinoma cells. Clin Cancer Res (2008) 1.02

A-ring-substituted estrogen-3-O-sulfamates: potent multitargeted anticancer agents. J Med Chem (2005) 1.02

Novel analogs of ghrelin: physiological and clinical implications. Eur J Endocrinol (2004) 1.01

Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats. Am J Physiol Endocrinol Metab (2008) 1.01

Rapid functional assays of recombinant IP3 receptors. Cell Calcium (2005) 0.99

Synthesis, antitubulin, and antiproliferative SAR of analogues of 2-methoxyestradiol-3,17-O,O-bis-sulfamate. J Med Chem (2010) 0.99

Benzothiazole derivatives as novel inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1. Mol Cell Endocrinol (2005) 0.98

2-MeOE2bisMATE and 2-EtE2bisMATE induce cell cycle arrest and apoptosis in breast cancer xenografts as shown by a novel ex vivo technique. Breast Cancer Res Treat (2007) 0.98

Genomic and proteomic microglial profiling: pathways for neuroprotective inflammatory responses following nerve fragment clearance and activation. J Neurochem (2007) 0.98

Inhibition of MCF-7 breast cancer cell proliferation and in vivo steroid sulphatase activity by 2-methoxyoestradiol-bis-sulphamate. J Steroid Biochem Mol Biol (2003) 0.98

Nicotinic acid adenine dinucleotide phosphate-mediated calcium signalling in effector T cells regulates autoimmunity of the central nervous system. Brain (2010) 0.98

Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. J Clin Endocrinol Metab (2007) 0.97

Inhibition of MDA-MB-231 cell cycle progression and cell proliferation by C-2-substituted oestradiol mono- and bis-3-O-sulphamates. Int J Cancer (2005) 0.97

Structure-activity relationships for pyrido-, imidazo-, pyrazolo-, pyrazino-, and pyrrolophenazinecarboxamides as topoisomerase-targeted anticancer agents. J Med Chem (2002) 0.97

Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model. J Cachexia Sarcopenia Muscle (2012) 0.95

Catalysis-associated conformational changes revealed by human CD38 complexed with a non-hydrolyzable substrate analog. J Biol Chem (2007) 0.95

Distinct functional properties of native somatostatin receptor subtype 5 compared with subtype 2 in the regulation of ACTH release by corticotroph tumor cells. Am J Physiol Endocrinol Metab (2005) 0.95

Steroid sulfatase: a new target for the endocrine therapy of breast cancer. Oncologist (2007) 0.94

Regulation of casein kinase-2 (CK2) activity by inositol phosphates. J Biol Chem (2004) 0.94

Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents. J Med Chem (2008) 0.94

Ghrelin, peptide YY and their hypothalamic targets differentially regulate spontaneous physical activity. Physiol Behav (2011) 0.94

Combined effects of ghrelin and higher food intake enhance skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rats with chronic kidney disease. Kidney Int (2010) 0.93

scyllo-inositol pentakisphosphate as an analogue of myo-inositol 1,3,4,5,6-pentakisphosphate: chemical synthesis, physicochemistry and biological applications. Chembiochem (2006) 0.93

Adenophostin A and analogues modified at the adenine moiety: synthesis, conformational analysis and biological activity. Org Biomol Chem (2004) 0.93

Rapid synthetic route toward structurally modified derivatives of cyclic adenosine 5'-diphosphate ribose. J Org Chem (2005) 0.93

Synthesis of stable and cell-type selective analogues of cyclic ADP-ribose, a Ca(2+)-mobilizing second messenger. Structure--activity relationship of the N1-ribose moiety. J Am Chem Soc (2005) 0.93

Biphenyl 2,3',4,5',6-pentakisphosphate, a novel inositol polyphosphate surrogate, modulates Ca2+ responses in rat hepatocytes. FASEB J (2007) 0.93

The enzymes of human diphosphoinositol polyphosphate metabolism. FEBS J (2013) 0.92

Chimeric microtubule disruptors. Chem Commun (Camb) (2010) 0.92

First synthetic analogues of diphosphoinositol polyphosphates: interaction with PP-InsP5 kinase. Chem Commun (Camb) (2012) 0.92

Synthesis and Ca2+-mobilizing activity of purine-modified mimics of adenophostin A: a model for the adenophostin-Ins(1,4,5)P3 receptor interaction. J Med Chem (2003) 0.92

Regioselective hydrolysis of myo-inositol 1,3,5-orthobenzoate via a 1,2-bridged 2'-phenyl-1',3'-dioxolan-2'-ylium ion provides a rapid route to the anticancer agent Ins(1,3,4,5,6)P5. Chem Commun (Camb) (2006) 0.92

Interactions of inositol 1,4,5-trisphosphate (IP(3)) receptors with synthetic poly(ethylene glycol)-linked dimers of IP(3) suggest close spacing of the IP(3)-binding sites. J Biol Chem (2002) 0.92

No effects of human ghrelin on cardiac function despite profound effects on body composition in a rat model of heart failure. Int J Cardiol (2008) 0.92

Binding of inositol 1,4,5-trisphosphate (IP3) and adenophostin A to the N-terminal region of the IP3 receptor: thermodynamic analysis using fluorescence polarization with a novel IP3 receptor ligand. Mol Pharmacol (2010) 0.92

A potential inhibitory role for the new truncated variant of somatostatin receptor 5, sst5TMD4, in pituitary adenomas poorly responsive to somatostatin analogs. J Clin Endocrinol Metab (2010) 0.92

Novel hydrolysis-resistant analogues of cyclic ADP-ribose: modification of the "northern" ribose and calcium release activity. Biochemistry (2002) 0.91

Drug Insight: prolactin-receptor antagonists, a novel approach to treatment of unresolved systemic and local hyperprolactinemia? Nat Clin Pract Endocrinol Metab (2006) 0.91

Structural basis for enzymatic evolution from a dedicated ADP-ribosyl cyclase to a multifunctional NAD hydrolase. J Biol Chem (2009) 0.91

Anti-cancer activities of novel D-ring modified 2-substituted estrogen-3-O-sulfamates. J Steroid Biochem Mol Biol (2005) 0.90

Somatostatin receptor subtype 1 selective activation in human growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas: effects on cell viability, GH, and PRL secretion. J Clin Endocrinol Metab (2003) 0.90

First enzymatic synthesis of an N1-cyclised cADPR (cyclic-ADP ribose) analogue with a hypoxanthine partial structure: discovery of a membrane permeant cADPR agonist. Chem Commun (Camb) (2003) 0.90

The effects of 2-substituted oestrogen sulphamates on the growth of prostate and ovarian cancer cells. J Steroid Biochem Mol Biol (2003) 0.90

A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140. Anticancer Res (2008) 0.90

Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules. Endocrinology (2007) 0.89

The use of steroid sulfatase inhibitors as a novel therapeutic strategy against hormone-dependent endometrial cancer. Endocrinology (2008) 0.89

A novel growth hormone secretagogue-1a receptor antagonist that blocks ghrelin-induced growth hormone secretion but induces increased body weight gain. Neuroendocrinology (2005) 0.89

Direct evidence for ArO-S bond cleavage upon inactivation of Pseudomonas aeruginosa arylsulfatase by aryl sulfamates. Chembiochem (2008) 0.89

Selective activation of somatostatin receptor subtypes differentially modulates secretion and viability in human medullary thyroid carcinoma primary cultures: potential clinical perspectives. J Clin Endocrinol Metab (2006) 0.89

Generation of nucleophilic character in the Cys25/His159 ion pair of papain involves Trp177 but not Asp158. Biochemistry (2008) 0.88

Activation of IP(3) receptors by synthetic bisphosphate ligands. Chem Commun (Camb) (2009) 0.88

Cell-permeant small-molecule modulators of NAADP-mediated Ca2+ release. Chem Biol (2006) 0.88

Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center study. Endocr Relat Cancer (2008) 0.87

Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin homology domain of protein kinase Balpha. ACS Chem Biol (2007) 0.87

Orvinols with mixed kappa/mu opioid receptor agonist activity. J Med Chem (2013) 0.87

Steroidomimetic Tetrahydroisoquinolines for the Design of New Microtubule Disruptors. ACS Med Chem Lett (2011) 0.87

Dual aromatase-steroid sulfatase inhibitors. J Med Chem (2007) 0.87

2-Alkylsulfanyl estrogen derivatives: synthesis of a novel class of multi-targeted anti-tumour agents. Bioorg Med Chem Lett (2004) 0.87

Constitutive somatostatin receptor activity determines tonic pituitary cell response. Mol Endocrinol (2009) 0.86

Suppression of L-type voltage-gated calcium channel-dependent synaptic plasticity by ethanol: analysis of miniature synaptic currents and dendritic calcium transients. J Pharmacol Exp Ther (2003) 0.86

Efficacy of three potent steroid sulfatase inhibitors: pre-clinical investigations for their use in the treatment of hormone-dependent breast cancer. Breast Cancer Res Treat (2007) 0.86

Structure-activity relationship for the first-in-class clinical steroid sulfatase inhibitor Irosustat (STX64, BN83495). ChemMedChem (2011) 0.86

A letrozole-based dual aromatase-sulphatase inhibitor with in vivo activity. J Steroid Biochem Mol Biol (2005) 0.86

Studies on pyrrolopyrimidines as selective inhibitors of multidrug-resistance-associated protein in multidrug resistance. J Med Chem (2004) 0.86

Steroid sulfatase: a pivotal player in estrogen synthesis and metabolism. Mol Cell Endocrinol (2011) 0.86

Chemoenzymatic synthesis of 7-deaza cyclic adenosine 5'-diphosphate ribose analogues, membrane-permeant modulators of intracellular calcium release. J Org Chem (2008) 0.86

Discovery of adamantyl ethanone derivatives as potent 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors. ChemMedChem (2010) 0.86