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Cenicriviroc
Cenicriviroc (INN, code names TAK-652, TBR-652, commonly abbreviated as CVC) is an experimental drug candidate for the treatment of HIV infection and in combination with Tropifexor for non-alcoholic steatohepatitis. It is being developed by Takeda and Tobira Therapeutics. Cenicriviroc is an inhibitor of CCR2 and CCR5 receptors, allowing it to function as an entry inhibitor which prevents the virus from entering into a human cell. Inhibition of CCR2 may have an anti-inflammatory effect. A double-blind, randomized, placebo-controlled clinical study to assess the antiviral activity, safety, and tolerability of cenicriviroc was conducted in 2010. HIV-infected patients taking cenicriviroc had significant reductions in viral load, with the effect persisting up to two weeks after discontinuation of treatment. Additional Phase II clinical trials are underway. Cenicriviroc is also in two separate clinical trials for COVID-19: the ACTIV-I trial run by the National Center for Advancing T ... [...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 bioc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vicriviroc
Vicriviroc, previously named SCH 417690 and SCH-D, is a pyrimidine CCR5 entry inhibitor of HIV-1. It was developed by the pharmaceutical company Schering-Plough. Merck & Co., Merck decided to not pursue regulatory approval for use in treatment-experienced patients because the drug did not meet primary efficacy endpoints in late stage trials. Clinical trials continue in patients previously untreated for HIV. HIV-1 background The mechanisms of a number of available anti-HIV drugs prevent either viral reverse transcriptase enzyme or protease enzyme, allowing the virus to enter the cell before these drugs take effect. However, CCR5 inhibitors such as vicriviroc, as well as other entry inhibitors of HIV-1, inhibit the initial stages of the virus life cycle. HIV-1 entry HIV binds to and fuses with the target T-cells or macrophages with the help of gp120 and gp41, the only two proteins that are currently known to be exhibited on the surface of the viral envelope. One molecule of ea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Discovery And Development Of CCR5-receptor Antagonists
CCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor CCR5 is involved in the process by which HIV, the virus that causes AIDS, enters cells. Hence antagonists of this receptor are entry inhibitors and have potential therapeutic applications in the treatment of HIV infections. The life cycle of the HIV presents potential targets for drug therapy, one of them being the viral entry pathway. CCR5 and CXCR4 are the main receptors involved in the HIV entry process. These receptors belong to the seven transmembrane G-protein-coupled receptor (GPCR) family and are predominantly expressed on human T-cells, dendritic cells and macrophages, Langerhans cells. They play an important role as co-receptors that HIV type 1 (HIV-1) uses to attach to cells before viral fusion and entry into host cells. HIV isolates can be divided into R5 and X4 strains. R5 strain is when the virus uses the co-receptor CCR5 and X4 strain is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mesylate
In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group or anion, the spelling used is sometimes mesilate (as in ''imatinib mesilate'', the mesylate salt of imatinib). Mesylate esters are a group of organic compounds that share a common functional group with the general structure , abbreviated , where R is an organic substituent. Mesylate is considered a leaving group in nucleophilic substitution reactions. Preparation Mesylates are generally prepared by treating an alcohol and methanesulfonyl chloride in the presence of a base, such as triethylamine. Mesyl Related to mesylate is the mesyl (Ms) or methanesulfonyl (CH3SO2) functional group. Methanesulfonyl chloride is often referred to as mesyl chloride. Whereas mesylates are often hydrolytically labile, mesyl groups, when attached to ni ... [...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 Medicin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Imidazoles
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non-adjacent nitrogen atoms in meta-substitution. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam. When fused to a pyrimidine ring, it forms a purine, which is the most widely occurring nitrogen-containing heterocycle in nature. The name "imidazole" was coined in 1887 by the German chemist Arthur Rudolf Hantzsch (1857–1935). Structure and properties Imidazole is a planar 5-membered r ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Entry Inhibitors
Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a cell, for example, by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D. HIV entry They are used in combination therapy for the treatment of HIV infection. This class of drugs interferes with the binding, fusion and entry of an HIV virion to a human cell. By blocking this step in HIV's replication cycle, such agents slow the progression from HIV infection to AIDS. Proteins There are several key proteins involved in the HIV entry process. * CD4, a protein receptor found on the surface of helper T cells in the human immune system, also called CD4+ T cells * gp120, a protein on HIV surface that binds to the CD4 receptor * CCR5, a second receptor found on the surface of CD4+ cells and macrophages, called a chemokine co-receptor * CXCR4, another chemokine co-receptor found on CD4+ cells * gp41, a HIV protein, closely ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Maraviroc
Maraviroc, sold under the brand names Selzentry (US) and Celsentri (EU), is an antiretroviral medication used to treat HIV infection. It is taken by mouth. It is in the CCR5 receptor antagonist class. It was approved for medical use in the United States in August 2007, and in the European Union in September 2007. Medical uses Maraviroc is indicated, in combination with other antiretroviral medications, for the treatment of only CCR5-tropic HIV-1 infection. Side effects Maraviroc can cause serious, life-threatening side effects. These include liver problems, skin reactions, and allergic reactions. An allergic reaction may happen before liver problems occur. Official labeling of Selzentry has black box warning for hepatotoxicity. The MOTIVATE trials showed no clinically relevant differences in safety between the maraviroc and placebo groups. Mechanism of action Maraviroc is an entry inhibitor. Specifically, maraviroc is a negative allosteric modulator of the CCR5 receptor, wh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD14
CD14 (cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP). CD14 exists in two forms, one anchored to the membrane by a glycosylphosphatidylinositol (GPI) tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa). The x-ray crystal structure of human CD14 reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket. CD14 was the first described pattern recognition receptor. Function CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS). CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein (LBP). Although LPS is considered its main ligand, CD14 also ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CCL2
''For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.'' The chemokine (C-C motif) ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 tightly regulates cellular mechanics and thereby recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection. Genomics In the human genome, CCL2 and many other CC chemokines are located on chromosome 17 (17q11.2-q21.1). The gene span is 1,927 bases and the CCL2 gene resides on the Watson (plus) strand. The CCL2 gene has three exons and two introns. The CCL2 protein precursor contains a signal peptide of 23 amino acids. In turn, the mature CCL2 is 76 amino acids long. The CCL2 predicted weight is 11.025 kiloDaltons (kDa). Population genetics In humans, the levels of CCL2 can vary considerably. In ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Charité
The Charité – Universitätsmedizin Berlin (Charité – Berlin University of Medicine) is one of Europe's largest university hospitals, affiliated with Humboldt University and Free University Berlin. With numerous Collaborative Research Centres of the German Research Foundation it is one of Germany's most research-intensive medical institutions. From 2012 to 2022, it was ranked by '' Focus'' as the best of over 1000 hospitals in Germany. In 2019 to 2022 ''Newsweek'' ranked the Charité as the 5th best hospital in the world, and the best in Europe. More than half of all German Nobel Prize winners in Physiology or Medicine, including Emil von Behring, Robert Koch and Paul Ehrlich, have worked at the Charité. Several politicians and diplomats have been treated at the Charité, including German Chancellor Angela Merkel, who underwent meniscus treatment at the Orthopaedic Department, Yulia Tymoshenko from Ukraine, and more recently Russian opposition leader Alexei Navalny, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
