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BET Inhibitors
BET inhibitors are a class of drugs that reversibly bind the bromodomains of Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and transcription factors. Discovery and development Thienodiazepine BET inhibitors were discovered by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted. However, these molecules remained largely unknown until 2010 when both the use of JQ1 in NUT midline carcinoma and of I-BET 762 in sepsis were published. Since this time a number of molecules have been described that are capable of targeting BET bromodomains. BET inhibitors have been described that are able to discriminate between the first and second bromodomains of BET proteins (BD1 vs BD2). However, no BET inhibitor has yet been described that can reliably distinguish ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bromodomain
A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine. Discovery The bromodomain was identified as a novel structural motif by John W. Tamkun and colleagues studying the drosophila gene ''Brahma''/''brm'', and showed sequence similarity to genes involved in transcriptional activation. The name "bromo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRAF Inhibitor
BRAF is a human gene that encodes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Raf. The B-Raf protein is involved in sending signals inside cells which are involved in directing cell growth. In 2002, it was shown to be mutated in some human cancers. Certain other inherited ''BRAF'' mutations cause birth defects. Drugs that treat cancers driven by ''BRAF'' mutations have been developed. Two of these drugs, vemurafenib and dabrafenib are approved by FDA for treatment of late-stage melanoma. Vemurafenib was the first approved drug to come out of fragment-based drug discovery. Function B-Raf is a member of the Raf kinase family of growth signal transduction protein kinases. This protein plays a role in regulating the MAP kinase/ ERKs signaling pathway, which affects cell division, differentiation, and secretion. S ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bromodomain
A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine. Discovery The bromodomain was identified as a novel structural motif by John W. Tamkun and colleagues studying the drosophila gene ''Brahma''/''brm'', and showed sequence similarity to genes involved in transcriptional activation. The name "bromo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
LY294002
LY294002 is a morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of phosphoinositide 3-kinases (PI3Ks). It is generally considered a non-selective research tool, and should not be used for experiments aiming to target PI3K uniquely. Two of these are the proto-oncogene serine/threonine-protein kinase (PIM1) and the phosphatidylinositol-4,5-bisphosphate 3-kinase P110 gamma, catalytic subunit gamma isoform. With an IC50 of 1.4 μM it is somewhat less potent than wortmannin, another well-known PI3 kinase inhibitor. However, LY294002 is a reversible inhibitor of PI3K whereas wortmannin acts irreversibly. Application of LY294002 causes a substantial acceleration of MEPP frequency (150 μM) at the frog neuromuscular junction through a mechanism that is independent of intraterminal calcium. LY294002 causes the release of MEPPs through a perturbation of synaptotagmin function. LY294002 is also a BET inhibitor (e.g. of BRD2, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oligodendrocyte Progenitor Cell
Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes. They are typically identified by coexpression of PDGFRA and NG2. OPCs play a critical role in developmental and adult myelinogenesis by giving rise to oligodendrocytes, which then ensheath axons and provide electrical insulation in the form of a myelin sheath, enabling faster action potential propagation and high fidelity transmission without a need for an increase in axonal diameter. The loss or lack of OPCs, and consequent lack of differentiated oligodendrocytes, is associated with a loss of myelination and subsequent impairment of neurological functions. In addition, OPCs express receptors for various neurotransmitters and undergo membrane depolarization when they receive synaptic inputs from neurons. Structure OPCs are glial cells ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Olinone
BET inhibitors are a class of drugs that reversibly bind the bromodomains of Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and transcription factors. Discovery and development Thienodiazepine BET inhibitors were discovered by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted. However, these molecules remained largely unknown until 2010 when both the use of JQ1 in NUT midline carcinoma and of I-BET 762 in sepsis were published. Since this time a number of molecules have been described that are capable of targeting BET bromodomains. BET inhibitors have been described that are able to discriminate between the first and second bromodomains of BET proteins (BD1 vs BD2). However, no BET inhibitor has yet been described that can reliably distinguish ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CPI-0610
CPI-0610 is a drug which acts as a BET inhibitor, mainly acting at the BRD2 and BRD4 subtypes. It has potential applications in the treatment of various forms of cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b .... References {{antineoplastic-drug-stub Antineoplastic and immunomodulating drugs Benzazepines ... [...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: ''Keytruda'' ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tenth largest pharmaceutical company and #294 on the 2022 ''Fortune'' Global 500, ranked behind other pharmaceutical companies China Resources, Sinopharm, Johnson & Johnson, Pfizer, Roche, AbbVie, Novartis, Bayer, and Merck. The company has a primary listing on the London Stock Exchange and is a constituent of the FTSE 100 Index. , it had a market capitalisation of £70 billion, the eighth largest on the London Stock Exchange. It has a secondary listing on the New York Stock Exchange. The company developed the first malaria vaccine, RTS,S, which it said in 2014 it would make available for five percent above cost. Legacy products developed at GSK include several listed in the World Health Organization's List of Essential Medicines, such ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
