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Torcetrapib
Torcetrapib (CP-529,414, Pfizer) was a drug being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Its development was halted in 2006 when phase III studies showed excessive all-cause mortality in the treatment group receiving a combination of atorvastatin (Lipitor) and torcetrapib. Medical uses Torcetrapib has not been found to reduce either cardiovascular disease or risk of death in those already taking a statin drug. Mechanism Torcetrapib acts (as a CETP inhibitor) by inhibiting cholesterylester transfer protein (CETP), which normally transfers cholesterol from HDL cholesterol to very low density or low density lipoproteins (VLDL or LDL). Inhibition of this process results in higher HDL cholesterol levels and reduces LDL cholesterol levels. According to Harvard Heart Letter: "HDL cholesterol is turning out to be a much more complex substance than we once believed. Instead of a single kind of particle, HDL cholest ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Torcetrapib Synthesis
Torcetrapib (CP-529,414, Pfizer) was a drug being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Its development was halted in 2006 when phase III studies showed excessive all-cause mortality in the treatment group receiving a combination of atorvastatin (Lipitor) and torcetrapib. Medical uses Torcetrapib has not been found to reduce either cardiovascular disease or risk of death in those already taking a statin drug. Mechanism Torcetrapib acts (as a CETP inhibitor) by inhibiting cholesterylester transfer protein (CETP), which normally transfers cholesterol from HDL cholesterol to very low density or low density lipoproteins (VLDL or LDL). Inhibition of this process results in higher HDL cholesterol levels and reduces LDL cholesterol levels. According to Harvard Heart Letter: "HDL cholesterol is turning out to be a much more complex substance than we once believed. Instead of a single kind of particle, HDL cholesterol is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cholesterylester Transfer Protein
Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-density (VLDL) or Chylomicrons and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a heteroexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride. Genetics The ''CETP'' gene is located on the sixteenth chromosome (16q21). Protein Fold The crystal structure of CETP is that of dimer of two TUbular LIPid (TULIP) binding domains. Each domain consists of a core of 6 elements: 4 beta-sheets forming an extended superhelix; 2 flanking elements that tend to include some alpha helix. The sheets wrap around the helices to produce a cylinder 6 x 2.5 x 2.5 nm. CETP contains two of these domains that interact head-to-hea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CETP Inhibitor
A CETP inhibitor is a member of a class of drugs that inhibit cholesterylester transfer protein (CETP). They are intended to reduce the risk of atherosclerosis (a cardiovascular disease) by improving blood lipid levels. At least three medications within this class have failed to demonstrate a beneficial effect. Types These drugs have generally failed in clinical trials, either causing a marked increase in deaths (torcetrapib), or having no meaningful clinical improvement despite HDL increases (dalcetrapib, evacetrapib). Failed: * Torcetrapib, failed in 2006 due to excess deaths in Phase III clinical trials. * Dalcetrapib, development halted in May 2012 when Phase III trials failed to show clinically meaningful efficacy. * Evacetrapib, development discontinued in 2015 due to insufficient efficacy. * Obicetrapib (TA-8995, AMG-899), Phase II results reported in 2015, discontinued in 2017 Succeeded: * Anacetrapib. In 2017, the REVEAL trial based on more than 30,000 participants sh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pfizer
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer (1824–1906) and his cousin Charles F. Erhart (1821–1891). Pfizer develops and produces medicines and vaccines for immunology, oncology, cardiology, endocrinology, and neurology. The company has several blockbuster drugs or products that each generate more than billion in annual revenues. In 2020, 52% of the company's revenues came from the United States, 6% came from each of China and Japan, and 36% came from other countries. Pfizer was a component of the Dow Jones Industrial Average stock market index from 2004 to August 2020. The company ranks 64th on the Fortune 500 and 49th on the Forbes Global 2000. History 1849–1950: Early history Pfizer was founded in 1849 by Charles Pfizer and Charles F. Erhart, two cousins w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dalcetrapib
Dalcetrapib (INN, codenamed JTT-705) is a CETP inhibitor which was being developed by Hoffmann–La Roche until May 2012. The drug was aimed at raising the blood levels of HDL cholesterol. Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health. A 24-week clinical trial showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect. Further, the dal-PLAQUE phase IIb trial found evidence of plaque reduction. Plaque reduction is an anticipated observation following an increase in HDL. five phase II trials had started and there was no evidence of the raised blood pressure seen with torcetrapib. dal-VESSEL phase IIb trial found no evidence of flow-mediated dilatation improvement. A 17% increase of Lp-PLA2 mass level was noted. Lp-PLA2 is associated with coronary heart disease and stroke. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over severa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
High-density Lipoprotein
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules ( lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle (organized by one, two or three ApoA. HDL particles enlarge while circulating in the blood, aggregating more fat molecules) and transporting up to hundreds of fat molecules per particle. Overview Lipoproteins are divided into five subgroups, by density/size (an inverse relationship), which also correlates with function and incidence of cardiovascular events. Unlike the larger lipoprotein particles, which deliver fat molecules to cells, HDL particles remove fat molecules from cells. The lipids carried include cholesterol, phospholipids, and triglycerides, amounts of each are variable. Increasing concentrations of HDL particles are associated with decreasing accumulation of atheroscl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Merck & Co
Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp & Dohme or MSD outside the United States and Canada. Merck & Co. was originally established as the American affiliate of Merck Group in 1891. Merck develops and produces medicines, vaccines, biologic therapies and animal health products. It has multiple blockbuster drugs or products each with 2020 revenues including cancer immunotherapy, anti-diabetic medication and vaccines against HPV and chickenpox. The company is ranked 71st on the 2022 ''Fortune'' 500 and 87th on the 2022 ''Forbes'' Global 2000, both based on 2021 revenues. Products The company develops medicines, vaccines, biologic therapies and animal health products. In 2020, the company had 6 blockbuster drugs or products, each with over $1 billion in revenue: ''Keytrud ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anacetrapib
Anacetrapib is a CETP inhibitor which was being developed to treat elevated cholesterol levels in an effort to prevent cardiovascular disease. In 2017 its development was abandoned by Merck. Evidence In 2017 REVEAL trial anacetrapib was shown to decrease the risk of repeat heart attacks in high-risk patients with previous acute coronary events. See also Other CETP inhibitors: *Torcetrapib was developed by Pfizer until December 2006 but caused unacceptable increases in blood pressure and had net cardiovascular detriment. *Dalcetrapib was developed by Hoffmann–La Roche until May 2012. It did not raise blood pressure and did raise HDL, but it showed no clinically meaningful efficacy. *Evacetrapib was developed by Eli Lilly & Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel .. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sodium Triacetoxyborohydride
Sodium triacetoxyborohydride, also known as sodium triacetoxyhydroborate, commonly abbreviated STAB, is a chemical compound with the formula Na(CH3COO)3BH. Like other borohydrides, it is used as a reducing agent in organic synthesis. This colourless salt is prepared by protonolysis of sodium borohydride with acetic acid: :NaBH4 + 3 HO2CCH3 → NaBH(O2CCH3)3 + 3 H2 Comparison with related reagents Sodium triacetoxyborohydride is a milder reducing agent than sodium borohydride or even sodium cyanoborohydride. It reduces aldehydes but not most ketones. It is especially suitable for reductive aminations of aldehydes and ketones. However, unlike sodium cyanoborohydride, the triacetoxyborohydride hydrolyzes readily, nor is it compatible with methanol. It reacts only slowly with ethanol and isopropanol and can be used with these. NaBH(OAc)3 may also be used for reductive alkylation of secondary amines with aldehyde-bisulfite adducts. Monoacetoxyborohydride The combinatio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Palladium
Palladium is a chemical element with the symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1803 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas, which was itself named after the epithet of the Greek goddess Athena, acquired by her when she slew Pallas. Palladium, platinum, rhodium, ruthenium, iridium and osmium form a group of elements referred to as the platinum group metals (PGMs). They have similar chemical properties, but palladium has the lowest melting point and is the least dense of them. More than half the supply of palladium and its congener platinum is used in catalytic converters, which convert as much as 90% of the harmful gases in automobile exhaust (hydrocarbons, carbon monoxide, and nitrogen dioxide) into nontoxic substances (nitrogen, carbon dioxide and water vapor). Palladium is also used in electronics, dentistry, medicine, hydrogen purification, chemical applications, groundwat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ammonium Formate
Ammonium formate, NH4HCO2, is the ammonium salt of formic acid. It is a colorless, hygroscopic, crystalline solid. Reductive amination Acetone can be transformed into isopropylamine as follows: :CH3C(O)CH3 + 2 HCO2− +NH4 → (CH3)2CHNHCHO + 2 H2O + NH3 + CO2 :(CH3)2CHNHCHO + H2O → (CH3)2CHNH2 + HCO2H Uses Pure ammonium formate decomposes into formamide and water when heated, and this is its primary use in industry. Formic acid can also be obtained by reacting ammonium formate with a dilute acid, and since ammonium formate is also produced from formic acid, it can serve as a way of storing formic acid. Ammonium formate can also be used in palladium on carbon (Pd/C) reduction of functional groups. In the presence of Pd/C, ammonium formate decomposes to hydrogen, carbon dioxide, and ammonia. This hydrogen gas is adsorbed onto the surface of the palladium metal, where it can react with various functional groups. For example, alkenes can be reduced to alkanes, formaldehyde to m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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