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Farnesoid X Receptor
The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the ''NR1H4'' gene in humans. Function FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes. One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 gene. In this way, a negative feedback ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nuclear Receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of specific genes thereby controlling the development, homeostasis, and metabolism of the organism. Nuclear receptors bind directly to DNA regulating the expression of adjacent genes; hence these receptors are classified as transcription factors. The regulation of gene expression by nuclear receptors often occurs in the presence of a ligand—a molecule that affects the receptor's behavior. Ligand binding to a nuclear receptor results in a conformational change activating the receptor. The result is up- or down-regulation of gene expression. A unique property of nuclear receptors that differentiates them from other classes of receptors is their direct control of genomic DNA. Nuclear receptors play key roles in both embryonic development a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peroxisome Proliferator-activated Receptor Alpha
Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the ''PPARA'' gene. Together with peroxisome proliferator-activated receptor delta and peroxisome proliferator-activated receptor gamma, PPAR-alpha is part of the subfamily of peroxisome proliferator-activated receptors. It was the first member of the PPAR family to be cloned in 1990 by Stephen Green and has been identified as the nuclear receptor for a diverse class of rodent Liver, hepatocarcinogens that causes proliferation of peroxisomes. Expression PPAR-α is primarily activated through ligand binding. Endogenous ligands include fatty acids such as arachidonic acid as well as other polyunsaturated fatty acids and various fatty acid-derived compounds such as certain members of the 15-hydroxyicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid family ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Guggulsterone
Guggulsterone is a phytosteroid found in the resin of the guggul plant, ''Commiphora mukul''. Guggulsterone can exist as either of two stereoisomers, ''E''-guggulsterone and ''Z''-guggulsterone. In humans, it acts as an antagonist of the farnesoid X receptor, which was once believed to result in decreased cholesterol synthesis in the liver. Several studies have been published that indicate no overall reduction in total cholesterol occurs using various dosages of guggulsterone, and levels of low-density lipoprotein ("bad cholesterol") increased in many people. Nevertheless, guggulsterone is an ingredient in many nutritional supplements. Guggulsterone was also found to have interactions with the viral Adipose Ribose Phosphatase enzyme of SARS-CoV2 and can prove to be a potential candidate for the development of therapeutics for the treatment of COVID19.Kciuk, M.; Mujwar, S.; Rani, I.; Munjal, K.; Gielecińska, A.; Kontek, R.; Shah, K. Computational Bioprospecting Guggulsterone a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tropifexor
Tropifexor is an investigational drug which acts as an agonist of the farnesoid X receptor (FXR). It was discovered by researchers from Novartis and Genomics Institute of the Novartis Research Foundation. Its synthesis and pharmacological properties were published in 2017. It was developed for the treatment of cholestatic liver diseases and nonalcoholic steatohepatitis (NASH). In combination with cenicriviroc, a CCR2 and CCR5 receptor inhibitor, it is undergoing a phase II clinical trial for NASH and liver fibrosis. Rats treated orally with tropifexor (0.03 to 1 mg/kg) showed an upregulation of the FXR target genes, BSEP and SHP, and a down-regulation of CYP8B1. Its EC50 ] Half maximal effective concentration (EC50) is a measure of the concentration of a drug, antibody or toxicant which induces a Stimulus%E2%80%93response_model, response halfway between the baseline and maximum after a specified exposure time. Mo ... for FXR is between 0.2 and 0.26 nM depending on the biochem ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Obeticholic Acid
Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma. Invention and development The natural bile acid chenodeoxycholic acid was identified in 1999 as the most active physiological ligand for the farnesoid X receptor (FXR), which is involved in many physiological and pathological processes. A series of alkylated bile acid analogues were designed, studied and patented by Roberto Pellicciari and colleagues at the University of Perugia, with 6α-ethyl-chenodeoxycholic acid emerging as the most highly potent FXR agonist. FXR-dependent processes in liver and intestine were proposed as therapeutic targets in human diseases. Obeticholic acid is the first FXR agon ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ivermectin
Ivermectin (, '' EYE-vər-MEK-tin'') is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, today it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. It works through many mechanisms to kill the targeted parasites, and can be taken orally, or applied to the skin for external infestations. It belongs to the avermectin family of medications. William Campbell and Satoshi Ōmura won the 2015 Nobel Prize in Physiology or Medicine for its discovery and applications. It is on the World Health Organization's List of Essential Medicines, and is approved by the U.S. Food and Drug Administration as an antiparasitic agent. In 2018, it was the 420th most commonly prescribed medication in the United States, with more than 100,000 prescriptions. It is availab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GW 4064
GW may refer to: People * George Washington, the first president of the United States * Gene Wilder, American actor and comedian Places * Gawok railway station, a railway station in Indonesia (station code) * George Washington Bridge across the Hudson River * Guinea-Bissau, by ISO country code Education *George Washington University, in Washington, D.C. **GW Law School in Washington, D.C. ** GW Business School ** GW School of Engineering & Applied Science **George Washington University Hospital in Washington, D.C. Arts and media * GateWorld, an English-language fan-news webpage * ''Gazeta Wyborcza'', a Polish newspaper *''Ghost Whisperer'', a CBS television show, 2005–2010 * Ghostwriter, a person hired to author texts that are credited to another person *''Golden Words'', a student publication of Queen's University in Kingston, Ontario * ''Guild Wars'', an episodic series of multiplayer online role-playing games Science and technology * .gw, the Internet top-level domain of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fexaramine
Fexaramine is an investigational compound which acts as an agonist of the farnesoid X receptor (FXR), which is a bile acid-activated nuclear receptor that controls bile-acid synthesis, conjugation and transport, as well as lipid metabolism through actions in the liver and intestine. The first publication about fexaramine in 2003 showed it has 100-fold greater affinity for FXR than natural compounds and described the genomic targets and binding site on FXR.; When administered orally to mice, fexaramine produced selective actions through FXR receptors in the intestines. Consistent with the effects of other FXR agonist drugs, in a study in mice, oral fexaramine stimulated intestinal fibroblast growth factor 15 (FGF15 Fibroblast growth factor 15 is a protein in mouse encoded by the ''Fgf15'' gene. It is a member of the fibroblast growth factor (FGF) family but, like FGF19, FGF21 and FGF23, has endocrine functions. FGF19 is the orthologous protein in humans. ...) production and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cafestol
Cafestol is a diterpenoid molecule present in coffee beans. It is one of the compounds that may be responsible for proposed biological and pharmacological effects of coffee. Sources A typical bean of '' Coffea arabica'' contains about 0.4-0.7% cafestol by weight. Cafestol is present in highest quantity in unfiltered coffee drinks such as French press coffee or Turkish coffee/ Greek coffee. In filtered coffee drinks such as drip brewed coffee, it is present in only negligible amounts, as the paper filter in drip filtered coffee retains the diterpenes. Research into biological activity Coffee consumption has been associated with a number of effects on health and cafestol has been proposed to produce these through a number of biological actions. Studies have shown that regular consumption of boiled coffee increases serum cholesterol whereas filtered coffee does not. Cafestol may act as an agonist ligand for the nuclear receptor farnesoid X receptor and pregnane X receptor, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Future Medicinal Chemistry
''Future Medicinal Chemistry'' is a peer-reviewed medical journal covering all aspects of medicinal chemistry, including drug discovery, pharmacology, in silico drug design, structural characterization techniques, ADME-Tox investigations, and science policy, economic and intellectual property issues. It was established in 2009 and is published by Future Science. The editors-in-chief are Iwao Ojima (The State University of New York at Stony Brook) and Jonathan Baell (Monash University). Abstracting and indexing The journal is abstracted and indexed by BIOSIS Previews, Chemical Abstracts, Chemistry Citation Index, Embase/Excerpta Medica, Index Medicus/MEDLINE/PubMed, Science Citation Index Expanded, and Scopus. According to the ''Journal Citation Reports'', the journal has a 2020 impact factor The impact factor (IF) or journal impact factor (JIF) of an academic journal is a scientometric index calculated by Clarivate that reflects the yearly mean number of citations of arti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Retinoid X Receptor Alpha
Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 (nuclear receptor subfamily 2, group B, member 1) is a nuclear receptor that in humans is encoded by the ''RXRA'' gene. Function Retinoid X receptors (RXRs) and retinoic acid receptors (RARs), are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors exert their action by binding, as homodimers or heterodimers, to specific sequences in the promoters of target genes and regulating their transcription. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcription factors. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PPARGC1A
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a protein that in humans is encoded by the ''PPARGC1A'' gene. PPARGC1A is also known as human accelerated region 20 ( HAR20). It may, therefore, have played a key role in differentiating humans from apes. PGC-1α is the master regulator of mitochondrial biogenesis. PGC-1α is also the primary regulator of liver gluconeogenesis, inducing increased gene expression for gluconeogenesis. Function PGC-1α is a super strong gene that contains two promoters, and has 4 alternative splicings. PGC-1α is a transcriptional coactivator that regulates the genes involved in energy metabolism. It is the master regulator of mitochondrial biogenesis. This protein interacts with the nuclear receptor PPAR-γ, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activity of, cAMP response element-binding protein (CREB) and nuclear respir ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
