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PPARγ Agonist
PPAR agonists are drugs which act upon the peroxisome proliferator-activated receptor. They are used for the treatment of symptoms of the metabolic syndrome, mainly for lowering triglycerides and blood sugar. Classification PPAR-alpha and PPAR-gamma are the molecular targets of a number of marketed drugs. The main classes of PPAR agonists are: PPAR-alpha agonists An endogenous compound, 7(S)-Hydroxydocosahexaenoic Acid (7(S)-HDHA), which is a Docosanoid derivative of the omega-3 fatty acid DHA was isolated as an endogenous high affinity ligand for PPAR-alpha in the rat and mouse brain. The 7(S) enantiomer bound with micromolar affity to PPAR alpha with 10 fold higher affinity compared to the (R) enantiomer and could trigger dendritic activation. PPARα (alpha) is the main target of fibrate drugs, a class of amphipathic carboxylic acids ( clofibrate, gemfibrozil, ciprofibrate, bezafibrate, and fenofibrate). They were originally indicated for cholesterol disorders and more recen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thiazolidinedione
The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s. Mechanism of action Thiazolidinediones or TZDs act by activating PPARs (peroxisome proliferator-activated receptors), a group of nuclear receptors 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 specif ..., specific for ''PPARγ'' (PPAR-gamma, PPARG). They are thus the PPARG agonists subset of PPAR agonists. The endogenous ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor binds to DNA in complex with the retinoid X ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Saroglitazar
Saroglitazar (INN, trade name Lipaglyn) is a drug for the treatment of type 2 diabetes mellitus and dyslipidemia. It is approved for use in India by the Drug Controller General of India. Saroglitazar is indicated for the treatment of diabetic dyslipidemia and hypertriglyceridemia with type 2 diabetes mellitus not controlled by statin therapy. In clinical studies, saroglitazar has demonstrated reduction of triglycerides (TG), LDL cholesterol, VLDL cholesterol, non-HDL cholesterol and an increase in HDL cholesterol a characteristic hallmark of atherogenic diabetic dyslipidemia (ADD). It has also shown anti-diabetic medication properties by reducing the fasting plasma glucose and HBA1c in diabetes patients. Mechanism of action Saroglitazar is an insulin sensitizer. It is a first in class drug which acts as a dual PPAR agonist at the subtypes α (alpha) and γ (gamma) of the peroxisome proliferator-activated receptor (PPAR). Agonist action on PPARα lowers high blood triglycerides, a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tesaglitazar
Tesaglitazar (also known as AZ 242) is a dual peroxisome proliferator-activated receptor agonist with affinity to PPARα and PPARγ, proposed for the management of type 2 diabetes. The drug had completed several phase III clinical trials, however in May, 2006 AstraZeneca announced that it had discontinued further development. Cardiac toxicity of tesaglitazar is related to mitochondrial toxicity caused by decrease in PPARγ coactivator 1-α (PPARGC1A, PGC1α) and sirtuin 1 Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 (''S. cerevisiae''), referring to the fact t ... (SIRT1). References Abandoned drugs Carboxylic acids Phenol ethers PPAR agonists Benzosulfones {{gastrointestinal-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Muraglitazar
Muraglitazar (proposed tradename Pargluva) is a dual peroxisome proliferator-activated receptor agonist with affinity to PPARα and PPARγ. The drug had completed phase III clinical trials, however in May, 2006 Bristol-Myers Squibb announced that it had discontinued further development. Data on muraglitazar is relatively sparse due to the recent introduction of this agent. One double-blind randomized clinical trial comparing muraglitazar and pioglitazone found that the effects of the former were favourable in terms of HDL-C increase, decrease in total cholesterol, apolipoprotein B, triglycerides and a greater reduction in HbA1c ( ''p'' <0.0001 for all comparisons). However, the muraglitazar group had a higher all-cause mortality, greater incidence of and |
Aleglitazar
Aleglitazar is a peroxisome proliferator-activated receptor agonist (hence a PPAR modulator ) with affinity to PPARα and PPARγ, which was under development by Hoffmann–La Roche for the treatment of type II diabetes. It is no longer in phase III clinical trials The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases .... References Oxazoles Benzothiophenes Carboxylic acids Phenol ethers PPAR agonists Methoxy compounds {{gastrointestinal-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GW501516
GW501516 (also known as GW-501,516, GW1516, GSK-516, Cardarine, and on the black market as Endurobol) is a PPARδ receptor agonist that was invented in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s. It entered into clinical development as a drug candidate for metabolic and cardiovascular diseases, but was abandoned in 2007 because animal testing showed that the drug caused cancer to develop rapidly in several organs. In 2007, research was published showing that high doses of GW501516 given to mice dramatically improved their physical performance; the work was widely discussed in popular media, and led to a black market for the drug candidate and to its abuse by athletes as a doping agent. The World Anti-Doping Agency (WADA) developed a test for GW501516 and other related chemicals and added them to the prohibited list in 2009; it has issued additional warnings to athletes that GW501516 is not safe. History GW501516 was initially discovered durin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peroxisome Proliferator-activated Receptor Delta
Peroxisome proliferator-activated receptor delta (PPAR-delta), or (PPAR-beta), also known as Nuclear hormone receptor 1 (NUC1) is a nuclear receptor that in humans is encoded by the ''PPARD'' gene. This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. It was first identified in ''Xenopus'' in 1993. Function PPAR-delta is a nuclear hormone receptor that governs a variety of biological processes and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer. In muscle PPARD expression is increased by exercise, resulting in increased oxidative (fat-burning) capacity and an increase in type I fibers. Both PPAR-delta and AMPK agonists are regarded as exercise mimetics. In adipose tissue PPAR-β/δ increases both oxidation as well as uncoupling of oxidative phosphorylation. PPAR-delta may function as an integrator of transcription repression and nuclear receptor signaling. It activ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ABCA1
ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the ''cholesterol efflux regulatory protein'' (CERP) is a protein which in humans is encoded by the ''ABCA1'' gene. This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis. Tangier disease It was discovered that a mutation in the ABCA1 protein is responsible for causing Tangier disease by several groups in 1998. Gerd Schmitz's group in Germany and Michael Hayden's group in British Columbia were using standard genetics techniques and DNA from family pedigrees to locate the mutation. Richard Lawn's group at CV Therapeutics in Palo Alto, CA used cDNA microarrays, which were relatively new at the time, to assess gene expression profiles from cell lines created from normal and affected individuals. They showed cell lines from patients with Tangier's disease showed differential regulation of the ABCA1 gene. Subsequent sequencing of the gene identifie ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which Artery, arteries are affected. The exact cause is not known and is proposed to be multifactorial. Risk factors include dyslipidemia, abnormal cholesterol levels, elevated levels of inflammatory markers, high blood pressure, diabetes, smoking, obesity, family history, genetic, and an unhealthy diet. Atheroma, Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. The narrowing of Artery, arteries limits the flow of oxygen-rich blood to parts of the body. Diagnosis is based upon a physical exam, ele ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Indole
Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence. The amino acid tryptophan is an indole derivative and the precursor of the neurotransmitter serotonin. General properties and occurrence Indole is a solid at room temperature. It occurs naturally in human feces and has an intense fecal odor. At very low concentrations, however, it has a flowery smell, and is a constituent of many perfumes. It also occurs in coal tar. The corresponding substituent is called indolyl. Indole undergoes electrophilic substitution, mainly at position 3 (see diagra ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used by mouth or intravenously. It typically begins working within an hour. Common side effects include heartburn and a rash. Compared to other NSAIDs, it may have other side effects such as gastrointestinal bleeding. It increases the risk of heart failure, kidney failure, and liver failure. At low doses, it does not appear to increase the risk of heart attack; however, at higher doses it may. Ibuprofen can also worsen asthma. While whether it is safe in early pregnancy is unclear, it appears to be harmful in later pregnancy, so is not recommended. Like other NSAIDs, it works by inhibiting the production of prostaglandins by decreasing the activity of the enzyme cyclooxygenase (COX). Ibuprofen is a w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
