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Molecular Glue
Molecular glue refers to a class of chemical compounds or molecules that play a crucial role in binding and stabilizing Protein–protein interaction, protein-protein interactions in biological systems. These molecules act as "glue" by enhancing the affinity between proteins, ultimately influencing various cellular processes. Molecular glue compounds have gained significant attention in the fields of drug discovery, chemical biology, and fundamental research due to their potential to modulate protein interactions, and thus, impact various cellular pathways. They have unlocked avenues in medicine previously thought to be "undruggable". History The concept of "molecular glue" originated in the late 20th century, with immunosuppressants like cyclosporine A (CsA) and FK506 identified as pioneering examples. CsA, discovered in 1971 during routine screening for antifungal antibiotics, exhibited Immunosuppression, immunosuppressive properties by inhibiting the Peptidylprolyl isomeras ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemical Compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element is therefore not a compound. A compound can be transformed into a different substance by a chemical reaction, which may involve interactions with other substances. In this process, bonds between atoms may be broken and/or new bonds formed. There are four major types of compounds, distinguished by how the constituent atoms are bonded together. Molecular compounds are held together by covalent bonds; ionic compounds are held together by ionic bonds; intermetallic compounds are held together by metallic bonds; coordination complexes are held together by coordinate covalent bonds. Non-stoichiometric compounds form a disputed marginal case. A chemical formula specifies the number of atoms of each element in a compound molecule, using the s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FKBP1A
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 (tacrolimus) and rapamycin (sirolimus). It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels including the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. There is evidence of multiple alternatively spliced transcript variants for this gene, but the full length nature of some variants has not been determined. Interactions FKBP1A has b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ubiquitin Ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another thing (the substrate) by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases reg ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proteolysis Targeting Chimera
A proteolysis targeting chimera (PROTAC) is a heterobifunctional small molecule composed of two active domains and a linker, capable of removing specific unwanted proteins. Rather than acting as a conventional enzyme inhibitor, a PROTAC works by inducing selective intracellular proteolysis. PROTACs consist of two covalently linked protein-binding molecules: one capable of engaging an E3 ubiquitin ligase, and another that binds to a target protein meant for degradation. Recruitment of the E3 ligase to the target protein results in ubiquitination and subsequent degradation of the target protein via the proteasome. Because PROTACs need only to bind their targets with high selectivity (rather than inhibit the target protein's enzymatic activity), there are currently many efforts to retool previously ineffective inhibitor molecules as PROTACs for next-generation drugs. Initially described by Kathleen Sakamoto, Craig Crews and Ray Deshaies in 2001, the PROTAC technology has been applie ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Raymond J
Raymond is a male given name. It was borrowed into English from French (older French spellings were Reimund and Raimund, whereas the modern English and French spellings are identical). It originated as the Germanic ᚱᚨᚷᛁᚾᛗᚢᚾᛞ (''Raginmund'') or ᚱᛖᚷᛁᚾᛗᚢᚾᛞ (''Reginmund''). ''Ragin'' (Gothic) and ''regin'' (Old German) meant "counsel". The Old High German ''mund'' originally meant "hand", but came to mean "protection". This etymology suggests that the name originated in the Early Middle Ages, possibly from Latin. Alternatively, the name can also be derived from Germanic Hraidmund, the first element being ''Hraid'', possibly meaning "fame" (compare ''Hrod'', found in names such as Robert, Roderick, Rudolph, Roland, Rodney and Roger) and ''mund'' meaning "protector". Despite the German and French origins of the English name, some of its early uses in English documents appear in Latinized form. As a surname, its first recorded appearance in Bri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Craig M
__NOTOC__ Craig may refer to: Geology *Craig (landform), a rocky hill or mountain often having large casims or sharp intentations. People (and fictional characters) *Craig (surname) * Craig (given name) Places Scotland *Craig, Angus, aka Barony of Craigie United States *Craig, Alaska, a city *Craig, Colorado, a city *Craig, Indiana, an unincorporated place * Craig, Iowa, a city *Craig, Missouri, a city * Craig, Montana, an unincorporated place *Craig, Nebraska, a village *Craig, Ohio, an unincorporated community *Craig County, Virginia *Craig County, Oklahoma *Craig Township (other) (two places) Other uses *Craig (song) *Craig Electronics, a consumer electronics company * Craig Broadcast Systems, later Craig Media and finally Craig Wireless, a defunct Canadian media and communication company *Clan Craig, a Scottish clan *Craig tube, a piece of scientific apparatus See also *''Craig v. Boren'', a U.S. Supreme Court case * Justice Craig (other) *Craic ''C ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Monomer
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Monomers can be classified in many ways. They can be subdivided into two broad classes, depending on the kind of the polymer that they form. Monomers that participate in condensation polymerization have a different stoichiometry than monomers that participate in addition polymerization: : Other classifications include: *natural vs synthetic monomers, e.g. glycine vs caprolactam, respectively *polar vs nonpolar monomers, e.g. vinyl acetate vs ethylene, respectively *cyclic vs linear, e.g. ethylene oxide vs ethylene glycol, respectively The polymerization of one kind of monomer gives a homopolymer. Many polymers are copolymers, meaning that they are derived from two different monomers. In the case of condensation polymerizations, the r ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tubulin
Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoskeleton. Microtubules function in many essential cellular processes, including mitosis. Tubulin-binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division. In eukaryotes, there are six members of the tubulin superfamily, although not all are present in all species.Turk E, Wills AA, Kwon T, Sedzinski J, Wallingford JB, Stearns "Zeta-Tubulin Is a Member of a Conserved Tubulin Module and Is a Component of the Centriolar Basal Foot in Multiciliated Cells"Current Biology (2015) 25:2177-2183. Both α and β tubulins have a mass of around 50 kDa and are thus in a similar range compared to actin (with a mass of ~42 kDa). In contrast, tubulin polymers (microtubules) te ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Discodermolide
(+)-Discodermolide is a polyketide natural product found to stabilize microtubules. (+)-discodermolide was isolated by Gunasekera and his co-workers at the Harbor Branch Oceanographic Institute from the deep-sea sponge ''Discodermia dissoluta'' in 1990.Gunasekera, S. P.; Gunasekera, M.; Longley, R. E.; Schulte, G. K. ''J. Org. Chem.'' 1990, ''55'', 4912-4915. () (+)-Discodermolide was found to be a potent inhibitor of tumor cell growth in several MDR cancer cell lines. (+)-discodermolide also shows some unique characters, including a linear backbone structure, immunosuppressive properties both in vitro and in vivo,Longley, R. E.; Caddigan, D.; Harmody, D.; Gunasekera, M.; Gunasekera, S. P. Transplantation 1991, 52, 650-655.Longley, R. E.; Caddigan, D.; Harmody, D.; Gunasekera, M.; Gunasekera, S. P. Transplantation 1991, 52, 656-661. potent induction of an accelerated senescence phenotype,Klein, L.; Freeze, B. S.; Smith, A. B., III; Horwitz, S. B. Cell Cycle 2005, 4, 501–507. and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Death Receptor
The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors contain transmembrane domains (TMDs), although some can be cleaved into soluble forms (e.g. TNFR1), and some lack a TMD entirely (e.g. DcR3). In addition, most TNF receptors require specific adaptor protein such as TRADD, TRAF, RIP and FADD for downstream signalling. TNF receptors are primarily involved in apoptosis and inflammation, but they can also take part in other signal transduction pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in leukoc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dimerization (chemistry)
A dimer () ('' di-'', "two" + ''-mer'', "parts") is an oligomer consisting of two monomers joined by bonds that can be either strong or weak, covalent or intermolecular. Dimers also have significant implications in polymer chemistry, inorganic chemistry, and biochemistry. The term ''homodimer'' is used when the two molecules are identical (e.g. A–A) and ''heterodimer'' when they are not (e.g. A–B). The reverse of dimerization is often called dissociation. When two oppositely charged ions associate into dimers, they are referred to as ''Bjerrum pairs'', after Niels Bjerrum. Noncovalent dimers Anhydrous carboxylic acids form dimers by hydrogen bonding of the acidic hydrogen and the carbonyl oxygen. For example, acetic acid forms a dimer in the gas phase, where the monomer units are held together by hydrogen bonds. Under special conditions, most OH-containing molecules form dimers, e.g. the water dimer. Excimers and exciplexes are excited structures with a short lifetime. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
