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Susan Band Horwitz
Susan Band Horwitz is an American biochemist and professor at the Albert Einstein College of Medicine where she holds the Falkenstein chair in Cancer Research as well as co-chair of the department of Molecular Pharmacology. Horwitz is a pioneer in dissecting the mechanisms of action of chemotherapeutic drugs including camptothecin, epipodophyllotoxins, and bleomycin, and Paclitaxel, taxol. Horwitz's work on taxol in particular has brought her international recognition. Horwitz discovered that taxol binds to microtubules, resulting in arrest of the cell cycle in metaphase. Her work paved the way to using taxol and other microtubule binding agents as chemotherapeutics. Taxol remains widely used today, as a means to treat ovarian, breast, and lung cancer. However, since taxol is in short supply, Horwitz is directing studies in her lab to identify similar therapies in natural products. Personal life and education Susan Band Horwitz was born in Cambridge, Massachusetts in 1937. She ...
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Albert Einstein College Of Medicine
Albert Einstein College of Medicine is a research-intensive medical school located in the Morris Park neighborhood of the Bronx in New York City. Founded in 1953, Einstein operates as an independent degree-granting institution as part of the integrated health care system, Montefiore Health System (Montefiore Medicine), which includes affiliates such as Jacobi Medical Center. Admission to Einstein is highly competitive, with one of the lowest acceptance rates among medical schools in the United States (3.3% in 2021). Einstein ranks 13th among top U.S. medical schools for graduate success in academic medicine and biomedical research (i.e., awards, publications, grants, and clinical trials), and its NIH funding per investigator consistently ranks among the highest in the nation (7th among US universities in 2019). Einstein offers a M.D. program, a Ph.D. program in the biomedical sciences and clinical investigation, and two Master of Science (M.S.) degrees. In 2021, the MD ...
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Antifolate
Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR). Comparison of available agents Mechanism Many are primarily DHFR inhibitors, but raltitrexed is an inhibitor of thymidylate synthase, and pemetrexed inhibits both and a third enzyme. Antifolates act specifically during DNA and RNA synthesis, and thus are cytotoxic during the S-phase of the cell cycle. Thus, they have a greater toxic effect on rapidly dividing cells (suc ...
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Microtubule-associated Protein
In cell biology, microtubule-associated proteins (MAPs) are proteins that interact with the microtubules of the cellular cytoskeleton. MAPs are integral to: the stability of the cell and its internal structures and the transport of components within the cell Function MAPs bind to the tubulin subunits that make up microtubules to regulate their stability. A large variety of MAPs have been identified in many different cell types, and they have been found to carry out a wide range of functions. These include both stabilizing and destabilizing microtubules, guiding microtubules towards specific cellular locations, cross-linking microtubules and mediating the interactions of microtubules with other proteins in the cell. Within the cell, MAPs bind directly to the tubulin dimers of microtubules. This binding can occur with either polymerized or depolymerized tubulin, and in most cases leads to the stabilization of microtubule structure, further encouraging polymerization. Usually, it is th ...
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Allosteric Regulation
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric site'' or ''regulatory site''. Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change and/or a change in protein dynamics. Effectors that enhance the protein's activity are referred to as ''allosteric activators'', whereas those that decrease the protein's activity are called ''allosteric inhibitors''. Allosteric regulations are a natural example of control loops, such as feedback from downstream products or feedforward from upstream substrates. Long-range allostery is especially important in cell signaling. Allosteric regulation is also particularly important in the cell's ability to adjust enzyme activity. The term ''allostery'' comes from the Ancient Greek ''allos'' (), "other", and ''stereos ...
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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. an ...
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Cremophor
Kolliphor EL, formerly known as Cremophor EL, is the registered trademark of BASF Corp. for its version of polyethoxylated castor oil. It is prepared by reacting 35 moles of ethylene oxide with each mole of castor oil. The resulting product is a mixture (CAS number 61791-12-6): the major component is the material in which the hydroxyl groups of the castor oil triglyceride have ethoxylated with ethylene oxide to form polyethylene glycol ethers. Minor components are the polyethyelene glycol esters of ricinoleic acid, polyethyelene glycols and polyethyelene glycol ethers of glycerol. Kolliphor EL is a synthetic, nonionic surfactant used to stabilize emulsions of nonpolar materials in water. Kolliphor EL is an excipient or additive in drugs. Therapeutically, modern drugs are rarely given in a pure chemical state, so most active ingredients are combined with excipients or additives such as Kolliphor EL. Uses * Miconazole, anti-fungal * Docetaxel, anti-cancer * Aci-Jel (acetic ...
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Hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thus, prefer other neutral molecules and nonpolar solvents. Because water molecules are polar, hydrophobes do not dissolve well among them. Hydrophobic molecules in water often cluster together, forming micelles. Water on hydrophobic surfaces will exhibit a high contact angle. Examples of hydrophobic molecules include the alkanes, oils, fats, and greasy substances in general. Hydrophobic materials are used for oil removal from water, the management of oil spills, and chemical separation processes to remove non-polar substances from polar compounds. Hydrophobic is often used interchangeably with lipophilic, "fat-loving". However, the two terms are not synonymous. While hydrophobic substances are usually lipophilic, there are excepti ...
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Lawrence Berkeley National Laboratory
Lawrence Berkeley National Laboratory (LBNL), commonly referred to as the Berkeley Lab, is a United States national laboratory that is owned by, and conducts scientific research on behalf of, the United States Department of Energy. Located in the hills of Berkeley, California, the lab overlooks the campus of the University of California, Berkeley, and is managed by the University of California system. History 1931–1941 The laboratory was founded on August 26, 1931, by Ernest Lawrence, as the Radiation Laboratory of the University of California, Berkeley, associated with the Physics Department. It centered physics research around his new instrument, the cyclotron, a type of particle accelerator for which he was awarded the Nobel Prize in Physics in 1939. Throughout the 1930s, Lawrence pushed to create larger and larger machines for physics research, courting private philanthropists for funding. He was the first to develop a large team to build big projects to make discove ...
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Designer Drug
A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union as new psychoactive substances (NPS) as well as analogs of performance-enhancing drugs such as designer steroids. Some of these were originally synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects, and shorter duration (and possibly also because it is easier to apply for patents for new molecules) and were later co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories. Because the efficacy and safety of these substances have not been thoroughly evaluated in animal and human trials, the use of some of these drugs may result ...
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Depolymerization
Depolymerization (or depolymerisation) is the process of converting a polymer into a monomer or a mixture of monomers. This process is driven by an increase in entropy. Ceiling temperature The tendency of polymers to depolymerize is indicated by their ceiling temperature. At this temperature, the enthalpy of polymerization matches the entropy gained by converting a large molecule into monomers. Above the ceiling temperature, the rate of depolymerization is greater than the rate of polymerization, which inhibits the formation of the given polymer. Applications Depolymerization is a very common process. Digestion of food involves depolymerization of macromolecules, such as proteins. It is relevant to polymer recycling. Sometimes the depolymerization is well behaved, and clean monomers can be reclaimed and reused for making new plastic. In other cases, such as polyethylene, depolymerization gives a mixture of products. These products are, for polyethylene, ethylene, propylene ...
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Cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components, microfilaments, intermediate filaments and microtubules, and these are all capable of rapid growth or disassembly dependent on the cell's requirements. A multitude of functions can be performed by the cytoskeleton. Its primary function is to give the cell its shape and mechanical resistance to deformation, and through association with extracellular connective tissue and other cells it stabilizes entire tissues. The cytoskeleton can also contract, thereby deforming the cell and the cell's environment and allowing cells to migrate. Moreover, it is involved in many cell signaling pathways and in the uptake of extracellular material ( endocytosi ...
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