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Discovery And Development Of Non-nucleoside Reverse Transcriptase Inhibitors
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV). NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV. RT is one of the most popular targets in the field of antiretroviral drug development. Discovery and development of NNRTIs began in the late 1980s and in the end of 2009 four NNRTI had been approved by regulatory authorities and several others were undergoing clinical development. Drug resistance develops quickly if NNRTIs are administered as monotherapy and therefore NNRTIs are always given as part of combination therapy, the highly active antiretroviral therapy (HAART). History Acquired immunodeficiency syndrome (AIDS) is a leading cause of death in the world. It was identified as a disease in 1981. Two years later the etiology agent for AIDS, the HIV was described. HIV is a retrovirus and has two major serotypes, HIV-1 an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Non-nucleoside Reverse-transcriptase Inhibitor
Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses. Mechanism of action When HIV infects a cell, reverse transcriptase copies the viral single stranded RNA genome into a double-stranded viral DNA. The viral DNA is then integrated into the host chromosomal DNA, which then allows host cellular processes, such as transcription and translation, to reproduce the virus. RTIs block reverse transcriptase's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying. A similar process occurs with other types of viruses. The hepatitis B virus, for example, carries its genetic material in the form of DNA, and employs an RNA-dependent DNA polymerase to replicate. Some of the same compounds used as RTIs c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver. Nucleotides are composed of three subunit molecules: a nucleobase, a five-carbon sugar (ribose or deoxyribose), and a phosphate group consisting of one to three phosphates. The four nucleobases in DNA are guanine, adenine, cytosine and thymine; in RNA, uracil is used in place of thymine. Nucleotides also play a central role in metabolism at a fundamental, cellular level. They provide chemical energy—in the form of the nucleoside triphosphates, adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP) and uridine triphosphate (UTP)—throughout the cell for the many cellular func ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences (see non-coding DNA), and often a substantial fraction of 'junk' DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome. The study of the genome is called genomics. The genomes of many organisms have been sequenced and various regions have been annotated. The International Human Genome Project reported the sequence of the genome for ''Homo sapiens'' in 200The Human Genome Project although the initial "finished" sequence was missing 8% of the genome consisting mostly of repetitive sequences. With advancements in technology that could handle sequenci ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rilpivirine
Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency (pharmacology), potency, longer biological half-life, half-life and reduced adverse drug reaction, side-effect profile compared with older NNRTIs such as efavirenz. Medical uses In the US, rilpivirine is approved for treatment-naive patients with a viral load of 100,000 copies/mL or less at therapy initiation. It has to be combined with other drugs against HIV.Rilpivirine . Accessed 2021-02-23. In the European Union, rilpivirine is approved in combination with cabotegravir for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/ml) with their current antiretroviral treatment, and when the virus has not developed resistance to certain class of anti-HIV medicines called non-nucleoside revers ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Etravirine
Etravirine (ETR, brand name Intelence, formerly known as TMC125) is a drug used for the treatment of HIV. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. Etravirine is marketed by Janssen, a subsidiary of Johnson & Johnson. In January 2008, the Food and Drug Administration approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. It was also approved for use in Canada on April 1, 2008. Etravirine is licensed in the United States, Canada, Israel, Russia, Australia and the European Union, and is under regulatory review in Switzerland. Indications and dosage Etravirine, in combination with other anti-retrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretrovir ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tibotec
Tibotec was a pharmaceutical company with a focus on research and development for the treatment of infectious diseases such as HIV/AIDS and hepatitis C. The company was founded in 1994 and then acquired by Johnson & Johnson and merged into its Janssen Pharmaceuticals division in 2002. History In 1994, Rudi Pauwels of the Rega Institute for Medical Research founded Tibotec, together with his wife Carine Claeys, and their first co-workers Marie-Pierre de Béthune, Kurt Hertogs, and Hilde Azijn. In 1995 Paul Stoffels (Janssen Pharmaceuticals) joined Tibotec. The company was acquired by Johnson & Johnson in April 2002. The name of the company is derived from the ''tetrahydro-imidazo ,5,1-jk1,4]-benzodiazepine-2(1H)-one and -thione'' (TIBO) compounds discovered at the Rega Institute for Medical Research (Belgium). Drugs * Darunavir (TMC114, tradename Prezista), a protease inhibitor * Etravirine (TMC125, tradename Intelence), a non-nucleoside reverse transcriptase inhibitor (NNRTI) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Efavirenz
Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is sold both by itself and in combination as efavirenz/emtricitabine/tenofovir. It is taken by mouth. Common side effects include rash, nausea, headache, feeling tired, and trouble sleeping. Some of the rashes may be serious such as Stevens–Johnson syndrome. Other serious side effects include depression, thoughts of suicide, liver problems, and seizures. It is not safe for use during pregnancy. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and works by blocking the function of reverse transcriptase. Efavirenz was approved for medical use in the United States in 1998, and in the European Union in 1999. It is on the World Health Organization's List of Essential Medicines. A ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Delavirdine
Delavirdine (DLV) (brand name Rescriptor) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) marketed by ViiV Healthcare. It is used as part of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) type 1. It is presented as the mesylate. The recommended dosage is 400 mg, three times a day. Although delavirdine was approved by the U.S. Food and Drug Administration in 1997, its efficacy is lower than other NNRTIs, especially efavirenz, and it also has an inconvenient schedule. These factors have led the U.S. DHHS not to recommend its use as part of initial therapy.DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download froAIDSInfo) The risk of cross-resistance across the NNRTI class, as well as its complex set of drug interactions, make the place of delavirdine in second-line and salvage therapy unclear, and it is currently rarely used. I ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Boehringer Ingelheim
C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical companies, and the largest private one. Headquartered in Ingelheim, it operates globally with 146 affiliates and more than 47,700 employees. Unlike most large pharmaceutical companies which are listed, the company is private and fully owned by the Boehringer, Liebrecht and von Baumbach families. The company's key areas of interest are: respiratory diseases, metabolism, immunology, oncology and diseases of the central nervous system. Boehringer Ingelheim is a full member of the European Federation of Pharmaceutical Industries and Associations (EFPIA). The corporate logo of Boehringer Ingelheim depicts a stylized rendition of the central section of the imperial palace of Charlemagne. History 1885–1999 *1885: Albert Boehringer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nevirapine
Nevirapine (NVP), sold under the brand name Viramune among others, is a medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medications. It may be used to prevent mother to child spread during birth but is not recommended following other exposures. It is taken by mouth. Common side effects include rash, headache, nausea, feeling tired, and liver problems. The liver problems and skin rash may be severe and should be checked for during the first few months of treatment. It appears to be safe for use during pregnancy. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and works by blocking the function of reverse transcriptase. Nevirapine was approved for medical use in the United States in 1996. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. Medical uses Nevirapine is used in people six years of age and older infected with HIV- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Retroviruses
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus ''retro'' (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Although retroviruses have different subfamilies, they have three basic groups: the oncoretroviruses (oncogenic retroviruses), the lentiviruses (slow retroviruses) and the spumaviruses (foamy viruses). The oncoretroviruses are able to cause cancer in some species, the lentiviruse ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protease Inhibitors
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] |
