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Bevirimat
Bevirimat (research code MPC-4326) is an anti-HIV drug derived from a betulinic acid-like compound, first isolated from ''Syzygium claviflorum,'' a Chinese herb. It is believed to inhibit HIV by a novel mechanism, so-called maturation inhibition. It is not currently U.S. Food and Drug Administration (FDA) approved. It was originally developed by the pharmaceutical company Panacos and reached Phase IIb clinical trials. Myriad Genetics announced on January 21, 2009 the acquisition of all rights to bevirimat for $7M USD. On June 8, 2010 Myriad Genetics announced that it was halting the development of maturation inhibitors, including bevirimat, to focus more on their oncology portfolio. Pharmacokinetics According to the only currently available study, "the mean terminal elimination half-life of bevirimat ranged from 56.3 to 69.5 hours, and the mean clearance ranged from 173.9 to 185.8 mL/hour." Mechanism of action Like protease inhibitors, bevirimat and other maturation inhibito ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Maturation Inhibitor
The maturation inhibitors are a class of antiviral drugs for the treatment of infection with HIV. They act by interfering with the maturation of the virus. Specifically, drugs in this class disrupt the final step in the processing of the HIV-1 ''gag'' protein, the cleavage of its immediate precursor by the enzyme HIV-1 protease. Unlike the class of drugs known as protease inhibitors, maturation inhibitors bind the ''gag'' protein, not the protease. This leads to the formation of noninfectious, immature virus particles, incapable of infecting other cells. No other class of drugs shares this mechanism of action, thus maturation inhibitors retain inhibitory activity against HIV infections with resistance. There are no currently available drugs from the class; however several clinical trials have been conducted. The first maturation inhibitor to be studied in humans was bevirimat, another was MPC-9055 (vivecon). Both were developed by Myriad Genetics Myriad Genetics, Inc. is an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BMS-955176
BMS-955176 is an experimental second generation HIV maturation inhibitor under development by Bristol-Myers Squibb for use in the treatment of HIV infection. By blocking the maturation of the virus, it prevents viral reproduction in host CD4+ T cells. First generation maturation inhibitors such as bevirimat were ineffective against some naturally occurring changes (polymorphisms) in the Gag protease polyprotein; BMS-955176 has been selected to better tolerate gag polymorphisms. __TOC__ Studies Results of a phase 2a trial of BMS-955176 was reported at the 2015 Conference on Retroviruses and Opportunistic Infections The Conference on Retroviruses and Opportunistic Infections (CROI) is an annual scientific meeting devoted to the understanding, prevention and treatment of HIV/AIDS and the opportunistic infection An opportunistic infection is an infection ca ... (CROI). Investigators concluded that the drug was well tolerated and effective against HIV, including strains with ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Betulinic Acid
Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It is found in the bark of several species of plants, principally the white birch (''Betula pubescens'') from which it gets its name, but also the ber tree (''Ziziphus mauritiana''), selfheal (''Prunella vulgaris''), the tropical carnivorous plants '' Triphyophyllum peltatum'' and ''Ancistrocladus heyneanus'', '' Diospyros leucomelas'', a member of the persimmon family, '' Tetracera boiviniana'', the jambul (''Syzygium formosanum''), flowering quince (''Pseudocydonia sinensis'', former ''Chaenomeles sinensis KOEHNE''), (''Chaenomeles sinensis KOEHNE'' is now named ''Pseudocydonia sinensis'') rosemary, and ''Pulsatilla chinensis''. Antitumor activity In 1995, betulinic acid was reported as a selective inhibitor of human melanoma. Then i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is located in the quadrant (anatomy), right upper quadrant of the abdomen, below the thoracic diaphragm, diaphragm. Its other roles in metabolism include the regulation of Glycogen, glycogen storage, decomposition of red blood cells, and the production of hormones. The liver is an accessory digestive organ that produces bile, an alkaline fluid containing cholesterol and bile acids, which helps the fatty acid degradation, breakdown of fat. The gallbladder, a small pouch that sits just under the liver, stores bile produced by the liver which is later moved to the small intestine to complete digestion. The liver's highly specialized biological tissue, tissue, consisting mostly of hepatocytes, regulates a w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Translation (biology)
In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or endoplasmic reticulum synthesize proteins after the process of transcription (biology), transcription of DNA to RNA in the cell's nucleus (cell), nucleus. The entire process is called gene expression. In translation, mRNA, messenger RNA (mRNA) is decoded in a ribosome, outside the nucleus, to produce a specific amino acid chain, or polypeptide. The polypeptide later protein folding, folds into an Activation energy, active protein and performs its functions in the Cell (biology), cell. The ribosome facilitates decoding by inducing the binding of Base pair, complementary tRNA anticodon sequences to mRNA codons. The tRNAs carry specific amino acids that are chained together into a polypeptide as the mRNA passes through and is "read" by the ribosome. Translation proceeds in three phases: # Initiation: The ribosome assembles around the target mRNA. The first tRNA is attached a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Triterpenes
Triterpenes are a class of chemical compounds composed of three terpene units with the molecular formula C30H48; they may also be thought of as consisting of six isoprene units. Animals, plants and fungi all produce triterpenes, including squalene, the precursor to all steroids. Structures Triterpenes exist in a great variety of structures. Nearly 200 different skeletons have been identified. These skeletons may be broadly divided according to the number of rings present. In general pentacyclic structures (5 rings) tend to dominate. Squalene is biosynthesized through the head-to-head condensation of two farnesyl pyrophosphate units. This coupling converts a pair of C15 components into a C30 product. Squalene serves as precursor for the formation of many triterpenoids, including bacterial hopanoids and eukaryotic sterols. Triterpenoids By definition triterpenoids are triterpenes that possess heteroatoms, usually oxygen. The terms ''triterpene'' and ''triterpenoid'' oft ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Maturation Inhibitors
{{disambiguation ...
Maturation is the process of becoming mature; the emergence of individual and behavioral characteristics through growth processes over time. Maturation may refer to: Science * Developmental psychology * Foetal development * Maturity (geology), in petroleum geology * Maturation, as a threat to internal validity of an experiment * Tissue maturation, an aspect of developmental biology ** The final stages of cellular differentiation of cells, tissues, or organs See also * Expiration (other) * Maturity (other) * Mature (other) Mature is the adjectival form of maturity, as immature is the adjectival form of immaturity, which have several meanings. Mature or immature may also refer to: * Mature, a character from ''The King of Fighters'' series *"Mature 17+", a rating in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carboxylic Acids
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion. Examples and nomenclature Carboxylic acids are commonly identified by their trivial names. They at oftentimes have the suffix ''-ic acid''. IUPAC-recommended names also exist; in this system, carboxylic acids have an ''-oic acid'' suffix. For example, butyric acid (C3H7CO2H) is butanoic acid by IUPAC guidelines. For nomenclature of complex molecules containing a carboxylic acid, the carboxyl can be considered position one of the parent chain even if there are other substituents, such as 3-chloropropanoic acid. Alternately, it can be named as a "carboxy" or "carboxylic acid" substituent on another ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phase IIb
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] |
Group-specific Antigen
Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus (except ''Caulimoviridae''). It was named as such because scientists used to believe it was antigenic. Now it is known that it makes up the inner shell, not the envelope exposed outside. It makes up all the structural units of viral conformation and provides supportive framework for mature virion. All orthoretroviral ''gag'' proteins are processed by the protease (PR or ''pro'') into MA (matrix), CA (capsid), NC (nucleocapsid) parts, and sometimes more. If Gag fails to cleave into its subunits, virion fails to mature and remains uninfective. It comprises part of the ''gag-onc'' fusion protein. Gag in HIV Numbering system By convention, the HIV genome is numbered according to HIV-1 group M subtype B reference strain HXB2. Transcription and mRNA processing After a virus enters a target cell, the viral genome is integrated into the host cell chromatin. RNA polymer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clearance (medicine)
In pharmacology, clearance is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time. Usually, clearance is measured in L/h or mL/min. The quantity reflects the rate of drug elimination divided by plasma concentration. Excretion, on the other hand, is a measurement of the amount of a substance removed from the body per unit time (e.g., mg/min, μg/min, etc.). While clearance and excretion of a substance are related, they are not the same thing. The concept of clearance was described by Thomas Addis, a graduate of the University of Edinburgh Medical School. Substances in the body can be cleared by various organs, including the kidneys, liver, lungs, etc. Thus, total body clearance is equal to the sum clearance of the substance by each organ (e.g., renal clearance + hepatic clearance + lung clearance = total body clearance). For many drugs, however, clearance is solely a function of renal excretion. In these cases, clearance is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protease Inhibitor (pharmacology)
Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS and hepatitis C. These protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles. Protease inhibitors that have been developed and are currently used in clinical practice include: * Antiretroviral HIV-1 protease inhibitors—class stem ** Amprenavir ** Atazanavir ** Darunavir ** Fosamprenavir ** Indinavir ** Lopinavir ** Nelfinavir ** Ritonavir ** Saquinavir ** Tipranavir * Hepatitis C virus NS3/ 4A protease inhibitors—class stem ** Asunaprevir ** Boceprevir ** Grazoprevir ** Glecaprevir ** Paritaprevir ** Simeprevir ** Telaprevir * Severe acute respiratory syndrome coronavirus 2 3-chymotrypsin-like protease inhibitors ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
