Read by QxMD icon Read

Selective androgen receptor modulators

Elgene Lim, Gerard Tarulli, Neil Portman, Theresa Hickey, Wayne D Tilley, Carlo Palmieri
The estrogen receptor-α (herein called ER) is a nuclear sex steroid receptor (SSR) that is expressed in approximately 75% of breast cancers. Therapies that modulate ER action have substantially improved the survival of patients with ER-positive breast cancer, but resistance to treatment still remains a major clinical problem. Treating resistant breast cancer requires co-targeting of ER and alternate signalling pathways that contribute to resistance to improve the efficacy and benefit of currently available treatments...
October 11, 2016: Endocrine-related Cancer
Dante Rojas, Gaud Dervilly-Pinel, Nora Cesbron, Mylène Penot, Alexandre Sydor, Stéphanie Prévost, Bruno Le Bizec
Besides their development for therapeutic purposes, non-steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth associated pathways as ligands of androgenic receptors (AR). They present thus a potential for abuse in sports and food producing animals as an interesting alternative to anabolic androgenic steroids (AAS). These compounds are easily available and could therefore be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies have to be developed for specific and sensitive detection of these compounds in biological matrices...
October 11, 2016: Drug Testing and Analysis
Christian Görgens, Sven Guddat, Andreas Thomas, Philipp Wachsmuth, Anne-Katrin Orlovius, Gerd Sigmund, Mario Thevis, Wilhelm Schänzer
So far, in sports drug testing compounds of different classes are processed and measured using different screening procedures. The constantly increasing number of samples in doping analysis, as well as the large number of substances with doping related, pharmacological effects require the development of even more powerful assays than those already employed in sports drug testing, indispensably with reduced sample preparation procedures. The analysis of native urine samples after direct injection provides a promising analytical approach, which thereby possesses a broad applicability to many different compounds and their metabolites, without a time-consuming sample preparation...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
Suriyan Ponnusamy, Ryan D Sullivan, Thirumagal Thiyagarajan, Heather Tillmann, Robert H Getzenberg, Ramesh Narayanan
OBJECTIVES: To evaluate two selective androgen receptor modulators (SARMs) (GTx-024 and GTx-027) in a post-menopausal animal model in order to determine their effect on pelvic floor muscles. Stress urinary incontinence (SUI), a prevalent condition, is represented by an involuntary leakage of urine that results, at least in part, from weakened or damaged pelvic floor muscles and is triggered by physical stress. Current treatment options are limited with no oral therapies available. The pelvic floor is rich in androgen receptor and molecules with anabolic activity including (SARMs) may serve as therapeutic options for individuals with SUI...
September 28, 2016: Journal of Cellular Biochemistry
Zsofia Kiss, Paramita M Ghosh
The androgen receptor (AR) plays a key role in the development and progression of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out higher incidences of CaP in some select groups, such as airline pilots and night shift workers in comparison to those working regular hours. The common finding in these 'high-risk' groups was that they all experienced a deregulation of the body's internal circadian rhythm. Here we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression...
September 22, 2016: Endocrine-related Cancer
Ashley T Fancher, Yun Hua, Daniel P Camarco, David A Close, Christopher J Strock, Paul A Johnston
The continued activation of androgen receptor (AR) transcription and elevated expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator observed in prostate cancer (CaP) recurrence and the development of castration-resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors of AR-TIF2 protein-protein interactions (PPIs) to find new drug candidates. Small molecules can elicit tissue selective effects, because the cells of distinct tissues express different levels and cohorts of coregulatory proteins...
October 2016: Assay and Drug Development Technologies
Timothy K O'Rourke, Matthew S Wosnitzer
Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes...
October 2016: Current Urology Reports
Aydogan Aydogdu, Ronald S Swerdloff
INTRODUCTION: Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable. AREAS COVERED: The available literature of T and alternative treatments for male hypogonadism are discussed. EXPERT OPINION: Transdermal application of T gels are the most commonly used route of T administration...
September 2016: Expert Opinion on Emerging Drugs
Christopher Wu, Jason R Kovac
There has recently been renewed interest in novel clinical applications of the anabolic-androgenic steroid (AAS) testosterone and its synthetic derivatives, particularly given with the rising popularity of testosterone supplementation therapy (TST) for the treatment of male hypogonadism. In this manuscript, we provide a brief review of the history of AAS and discuss clinical applications of two of the more well-known AAS: nandrolone and oxandrolone. Both agents exhibit favorable myotrophic/androgenic ratios and have been investigated for effectiveness in numerous disease states...
October 2016: Current Urology Reports
Barbora Fialova, Petra Luzna, Jan Gursky, Katerina Langova, Zdenek Kolar, Katerina Smesny Trtkova
The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. Castration-resistant prostate cancer (CRPC) is a consequence of androgen deprivation therapy. Unchecked CRPC followed by metastasis is lethal. Some CRPCs show decreased AR gene expression due to epigenetic mechanisms such as DNA methylation and histone deacetylation. The aim of this study was to epigenetically modulate the methylated state of the AR gene leading to targeted demethylation and AR gene expression in androgen-independent human prostate cancer DU145 cell line, representing the CRPC model with very low or undetectable AR levels...
October 2016: Oncology Reports
Vishnu Lal Sharma, Sonal Gupta, Gopal Gupta
Proliferation of the smooth muscle and epithelial cells within the prostatic transition zone in older men leads to benign prostatic hyperplasia (BPH) which is hallmarked by the troublesome lower urinary tract symptoms. The affair responsible for the initiation and promotion of disease is still unresolved. Alpha blockers and 5α-reductase inhibitors are used as management options for relief of the dynamic and static components respectively. Combination therapy including both the alpha blocker and 5α-reductase inhibitors is emerging as inclusive parcel for treatment...
June 30, 2016: Mini Reviews in Medicinal Chemistry
Yu-Chi Li, Man-Ling Luo, Huan Guo, Tian-Tian Wang, Shou-Ren Lin, Jian-Bo Chen, Qian Ma, Yan-Li Gu, Zhi-Mao Jiang, Yao-Ting Gui
Nuclear receptor subfamily 0 group B member 1 (Nr0b1) is an atypical member of the nuclear receptor family that is predominantly expressed in mouse Sertoli cells (SCs). Mutations of NR0B1 in humans cause adrenal failure and hypogonadotropic hypogonadism. The targeted mutagenesis of Nr0b1 in mice has revealed a primary gonadal defect characterized by the overexpression of aromatase and cellular obstruction of the seminiferous tubules and efferent ductules, leading to germ cell death and infertility. The transgenic expression of Nr0b1 under the control of the Müllerian-inhibiting substance promoter (MIS-Nr0b1), which is selectively expressed in SCs, improves fertility...
September 2016: International Journal of Molecular Medicine
Andreas Lagojda, Dirk Kuehne, Oliver Krug, Andreas Thomas, Tina Wigger, Uwe Karst, Wilhelm Schänzer, Mario Thevis
Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus...
2016: European Journal of Mass Spectrometry
Kenta Watanabe, Michiko Hirata, Tsukasa Tominari, Chiho Matsumoto, Yasuyuki Endo, Gillian Murphy, Hideaki Nagase, Masaki Inada, Chisato Miyaura
Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321...
September 9, 2016: Biochemical and Biophysical Research Communications
Giorgio Secreto, Sabina Sieri, Claudia Agnoli, Sara Grioni, Paola Muti, Barnett Zumoff, Milena Sant, Elisabetta Meneghini, Vittorio Krogh
Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer...
August 2016: Breast Cancer Research and Treatment
Alessio Molfino, Maria Ida Amabile, Filippo Rossi Fanelli, Maurizio Muscaritoli
INTRODUCTION: Cachexia and sarcopenia are conditions phenotypically characterized by muscle loss and represent a factor of poor prognosis, increasing patients' morbidity and mortality. Cachectic and sarcopenic patients often suffer from low quality of life, presenting lower muscle strength and appetite loss, which makes research on novel treatment strategies to ameliorate clinical response including patient's symptoms, the objective of scientific interest. AREAS COVERED: This article covers recent developments in the area of cachexia and sarcopenia treatment and therapeutic interventions, targeting central nervous system involvement, key inflammatory and muscle-specific metabolic pathways...
October 2016: Expert Opinion on Biological Therapy
Raj Kumar
Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time...
September 2016: Asian Journal of Andrology
Eva De Mol, R Bryn Fenwick, Christopher T W Phang, Victor Buzón, Elzbieta Szulc, Alex de la Fuente, Albert Escobedo, Jesús García, Carlos W Bertoncini, Eva Estébanez-Perpiñá, Iain J McEwan, Antoni Riera, Xavier Salvatella
Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by which this compound exerts its inhibitory activity is however not yet fully understood. Here we show, by using high resolution solution nuclear magnetic resonance spectroscopy, that EPI-001 selectively interacts with a partially folded region of the transactivation domain of the androgen receptor, known as transactivation unit 5, that is key for the ability of prostate cells to proliferate in the absence of androgens, a distinctive feature of castration-resistant prostate cancer...
September 16, 2016: ACS Chemical Biology
Toshihiko Yanase
In recent years, the drugs, which show anabolic, effect on bone and muscle without stimulating prostate has been developed. They show tissue-specific selective androgen actions and called selective androgen receptor modulators(SARMs). The development of drug targeting bone and muscle in male is very promising as a treatment tool for osteoporosis and sarcopenia in the near future. The clinical study is under going especially in the field of cachexia associated with cancer, but unfortunately there is no drug in the current market at present...
July 2016: Clinical Calcium
Emanuela Corsini, Valentina Galbiati, Angela Papale, Elena Kummer, Antonella Pinto, Melania M Serafini, Antonio Guaita, Roberto Spezzano, Donatella Caruso, Marina Marinovich, Marco Racchi
BACKGROUND: Over the past fifteen years, we have demonstrated that cortisol and dehydroepiandrosterone (DHEA) have opposite effects on the regulation of protein kinase C (PKC) activity in the context of the immune system. The anti-glucocorticoid effect of DHEA is also related to the regulation of splicing of the glucocorticoid receptor (GR), promoting the expression of GRβ isoform, which acts as a negative dominant form on GRα activity. Moreover, it is very well known that DHEA can be metabolized to androgens like testosterone, dihydrotestosterone (DHT), and its metabolites 3α-diol and 3β-diol, which exert their function through the binding of the androgen receptor (AR)...
2016: Immunity & Ageing: I & A
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"