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Pracinostat
Pracinostat (SB939) is an orally bioavailable, small-molecule histone deacetylase (HDAC) inhibitor based on hydroxamic acid with potential anti-tumor activity characterized by favorable physicochemical, pharmaceutical, and pharmacokinetic properties. Activity Pracinostat selectively inhibits HDAC class I, II, IV without class III and HDAC6 in class IIb, but has no effect on other Zn-binding enzymes, receptors, and ion channels. It accumulates in tumor cells and exerts a continuous inhibition to histone deacetylase, resulting in acetylated histones accumulation, chromatin remodeling, tumor suppressor genes transcription, and ultimately, apoptosis of tumor cells. Clinical medication Clinical studies suggests that pracinostat has potential best pharmacokinetic properties when compared to other oral HDAC inhibitors. In March 2014, pracinostat has granted Orphan Drug for acute myelocytic leukemia (AML) and for the treatment of T-cell lymphoma by the Food and Drug Administration ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HDAC Inhibitor
Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. Since deacetylation of histones produces transcriptionally silenced heterochromatin, HDIs can render chromatin more transcriptionally active and induce epigenomic changes. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics, such as valproic acid. Since at least 2003 they have been investigated as possible treatments for cancers, parasitic and inflammatory diseases. Cellular biochemistry/pharmacology To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones. This is accomplished with the assistance of histone acetyl transferases (HAT), which acetylate the lysine residues in core histones leading to a less compact and more transcriptionally active euchromatin, and, on the converse, the actions of histone deacetylases (HDAC), which remove the acetyl groups from the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hydroxamic Acid
In organic chemistry, hydroxamic acids are a class of organic compounds having a general formula bearing the functional group , where R and R' are typically organyl groups (e.g., alkyl or aryl) or hydrogen. They are amides () wherein the nitrogen atom has a hydroxyl () substituent. They are often used as metal chelators. Common example of hydroxamic acid is aceto-''N''-methylhydroxamic acid (). Some uncommon examples of hydroxamic acids are formo-''N''-chlorohydroxamic acid () and chloroformo-''N''-methylhydroxamic acid (). Synthesis and reactions Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid ( or , where Ph is phenyl group), the overall equation is: : Hydroxamic acids can also be synthesized from aldehydes and ''N''-sulfonylhydroxylamine via the Angeli-Rimini reaction. Alternatively, molybdenum oxide diperoxide oxidizes trimethylsilated amides to hydroxamic acid ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transcription (genetics)
Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transcribed into RNA molecules called non-coding RNAs (ncRNAs). Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. In virology, the term transcription is used when referring to mRNA synthesis from a viral RNA molecule. The genome of many RNA viruses is composed of negative-sense RNA which acts as a template for positive sense viral messenger RNA - a necessary step in the synthesis of viral proteins needed for viral replication. This process is catalyzed by a viral RNA dependent RNA polymerase. Background A DNA transcription unit encoding ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biology), morphology) and death. These changes include Bleb (cell biology), blebbing, Plasmolysis, cell shrinkage, Karyorrhexis, nuclear fragmentation, Pyknosis, chromatin condensation, Apoptotic DNA fragmentation, DNA fragmentation, and mRNA decay. The average adult human loses 50 to 70 1,000,000,000, billion cells each day due to apoptosis. For the average human child between 8 and 14 years old, each day the approximate loss is 20 to 30 billion cells. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orphan Drug
An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by the conditions. The conditions that orphan drugs are used to treat are referred to as orphan diseases. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy that depends on the legislation (if there is any) of the country. Designation of a drug as an orphan drug has yielded medical breakthroughs that might not otherwise have been achieved, due to the economics of drug medical research, research and development. Examples of this can be that in the U.S. and the EU, it is easier to gain marketing approval for an orphan drug. There may be other financial incentives, such as an extended period of exclusivity, during which the producer has sole rights to market the drug. All are intended to en ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acute Myelocytic Leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated. Risk factors include getting older, being male, smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes for which treatments and outcom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T-cell Lymphoma
T-cell lymphoma is a rare form of cancerous lymphoma affecting T cell, T-cells. Lymphoma arises mainly from the uncontrolled proliferation of lymphocytes, such as T-cells, and can become cancerous. T-cell lymphoma is categorized under Non-Hodgkin lymphoma (NHL) and represents less than 15% of all Non-Hodgkin's diseases in the category. T-cell lymphomas are often categorised based on their growth patterns as either aggressive (fast-growing) or indolent (slow-growing). Although the cause of T-cell lymphoma is not definitive, it has been associated with various risk factors and viruses such as Epstein–Barr virus (EBV) and Human T cell leukemia virus-1, human T-cell leukemia virus-1 (HTLV1). The prognosis and treatment of T-cell lymphoma can vary drastically based on the specific type of lymphoma and its growth patterns. Due to their rarity and high variability between the different subtypes, the prognosis of T-cell lymphoma is significantly worse than other Non-Hodgkin lymphoma. Th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, Prescription drug, prescription and Over-the-counter drug, over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, Animal feed, animal foods & feed and Veterinary medicine, veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C). However, the agency also enforces other laws, notably Section 361 of the Public Health Service Act as well as associated regulations. Much of this regulatory-enforcement work is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Histone Deacetylase Inhibitors
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 9 micrometers (0.09 mm) of 30 nm diameter chromatin fibers. There are five families of histones, which are designated H1/H5 (linker histones), H2, H3, and H4 (core histones). The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer. The tight wrapp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Benzimidazoles
Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals. Preparation Benzimidazole was discovered during research on vitamin B12. The benzimidazole nucleus was found to be a stable platform on which drugs could be developed. Benzimidazole is produced by condensation of o-phenylenediamine with formic acid, or the equivalent trimethyl orthoformate: :C6H4(NH2)2 + HC(OCH3)3 → C6H4N(NH)CH + 3 CH3OH 2-Substituted derivatives are obtained when the condensation is conducted with aldehydes in place of formic acid, followed by oxidation. Reactions Benzimidazole is a base: :C6H4N(NH)CH + H+ → 6H4(NH)2CHsup>+ It can also be deprotonated with stronger bases: :C6H4N(NH)CH + LiH → Li 6H4N2CH + H2 The imine can be alkylated and also serves as a ligand in coordination chemistry. The most pro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hydroxamic Acids
In organic chemistry, hydroxamic acids are a class of organic compounds having a general formula bearing the functional group , where R and R' are typically organyl groups (e.g., alkyl or aryl) or hydrogen. They are amides () wherein the nitrogen atom has a hydroxyl () substituent. They are often used as metal chelation, chelators. Common example of hydroxamic acid is aceto-''N''-methylhydroxamic acid (). Some uncommon examples of hydroxamic acids are formo-''N''-chlorohydroxamic acid () and chloroformo-''N''-methylhydroxamic acid (). Synthesis and reactions Hydroxamic acids are usually prepared from either esters or acid chlorides by a reaction with hydroxylamine salts. For the synthesis of benzohydroxamic acid ( or , where Ph is phenyl group), the overall equation is: : Hydroxamic acids can also be synthesized from aldehydes and ''N''-sulfonylhydroxylamine via the Angeli-Rimini reaction. Alternatively, molybdenum oxide diperoxide oxidizes trimethylsilyl, trimethylsilated ami ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
