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Phototrexate
Phototrexate is a photochromic antifolate drug developed at the Institute for Bioengineering of Catalonia (IBEC, The Barcelona Institute of Science and Technology). In particular, it is a photopharmacological agent that behaves as light-regulated inhibitor of the dihydrofolate reductase (DHFR) enzyme. Phototrexate is a photoisomerizable structural analogue of the chemotherapy agent methotrexate. It is also an example of "azologization". Pharmacological effects of phototrexate can be switched on and off by UVA and visible light, respectively. Phototrexate is almost inactive in its ''trans'' configuration while it behaves as a potent antifolate in its ''cis'' configuration. It can also spontaneously self-deactivate in the dark. See also * Cancer * Psoriasis * Psoriatic arthritis Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire f ...
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Photopharmacology
Photopharmacology, an emerging approach in medicine, involves activating and deactivating photoswitchable molecules with light for target drug delivery. Clinicians use the energy of light to change the shape and chemical properties of a drug, resulting in different biological activity. This is done to ultimately achieve control of when and where drugs are active in a reversible manner, and to prevent side effects and exposure to the environment of antibiotics. Switching drugs "on" and "off" is achieved by introducing photoswitches such as azobenzene, spiropyran or diarylethene into the drug. Photopharmalogical drugs with a photoswitch have two different states, which light can toggle between. Since both states have a different structure, the activity of the drug is different, hence the "on" and "off" state of the drug. An example is photostatin, which is an inhibitor that can be switched on and off ''in vivo'' to optically control microtubule dynamics. See also * Optogenetics ...
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Photochromism
Photochromism is the reversible transformation of a chemical species (photoswitch) between two forms by the absorption of electromagnetic radiation (photoisomerization), where the two forms have different absorption spectra. In plain language, this can be described as a reversible change of color upon exposure to light. Applications Sunglasses One of the most famous reversible photochromic applications is color changing lenses for sunglasses. The largest limitation in using photochromic technology is that the materials cannot be made stable enough to withstand thousands of hours of outdoor exposure so long-term outdoor applications are not appropriate at this time. The switching speed of photochromic dyes is highly sensitive to the rigidity of the environment around the dye. As a result, they switch most rapidly in solution and slowest in the rigid environment like a polymer lens. In 2005 it was reported that attaching flexible polymers with low glass transition temperature (f ...
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Institute For Bioengineering Of Catalonia
The Institute for Bioengineering of Catalonia (IBEC) is an institution engaged in basic and applied research in bioengineering and nanomedicine, with experts working on tissue regeneration, biomechanics, molecular dynamics, biomimetics, drug delivery, organs ‘on-a-chip’, cell migration, stem cells, artificial olfaction and microbial biotechnology. The institute was created by the Government of Catalonia, the University of Barcelona and the Polytechnic University of Catalonia in December 2005 and is located at the Barcelona Science Park (Parc Científic de Barcelona – PCB). The director of the institute is Prof. Josep Samitier, who took over from founding director Josep A. Planell i Estany in 2013. In 2014 IBEC was named a "Severo Ochoa Centre of Excellence" by the Spanish Ministry of Economy and Competitiveness. Mission The institute aims to pursue interdisciplinary research in bioengineering and nanomedicine which is combined with specific transfer targets to produce new ap ...
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Dihydrofolate Reductase
Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In humans, the DHFR enzyme is encoded by the ''DHFR'' gene. It is found in the q11→q22 region of chromosome 5. Bacterial species possess distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar. Structure A central eight-stranded beta-pleated sheet makes up the main feature of the polypeptide backbone folding of DHFR. Seven of these strands are parallel and the eighth runs antiparallel. Four alpha helices connect successive beta strands. Residues 9 – 24 are termed "Met20" or "loop 1" and, along with other loops, are part of the major subdomain that surround the active site. The active site is situated in the N-terminal half of the sequence, which includes a conse ...
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Photoisomerization
In chemistry, photoisomerization is a form of isomerization induced by photoexcitation. Both reversible and irreversible photoisomerizations are known for photoswitchable compounds. The term "photoisomerization" usually, however, refers to a reversible process. Applications Photoisomerization of the compound retinal in the eye allows for vision. Photoisomerizable substrates have been put to practical use, for instance, in pigments for rewritable CDs, DVDs, and 3D optical data storage solutions. In addition, interest in photoisomerizable molecules has been aimed at molecular devices, such as molecular switches, molecular motors, and molecular electronics. Another class of device that uses the photoisomerization process is as an additive in liquid crystals to change their linear and nonlinear properties. Due to the photoisomerization is possible to induce a molecular reorientation in the liquid crystal bulk, which is used in holography, as spatial filter or optical switching. ...
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Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals (signal transduction). The development of therapies with specific molecular or genetic targets, wh ...
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Methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection. Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It acts by blocking the body's use of folic acid. Methotrexate was first made in 1947 and ...
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Ultraviolet
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight, and constitutes about 10% of the total electromagnetic radiation output from the Sun. It is also produced by electric arcs and specialized lights, such as mercury-vapor lamps, tanning lamps, and black lights. Although long-wavelength ultraviolet is not considered an ionizing radiation because its photons lack the energy to ionization, ionize atoms, it can cause chemical reactions and causes many substances to glow or fluorescence, fluoresce. Consequently, the chemical and biological effects of UV are greater than simple heating effects, and many practical applications of UV radiation derive from its interactions with organic molecules. Short-wave ultraviolet light damages DNA and sterilizes surf ...
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Light
Light or visible light is electromagnetic radiation that can be perceived by the human eye. Visible light is usually defined as having wavelengths in the range of 400–700 nanometres (nm), corresponding to frequencies of 750–420 terahertz, between the infrared (with longer wavelengths) and the ultraviolet (with shorter wavelengths). In physics, the term "light" may refer more broadly to electromagnetic radiation of any wavelength, whether visible or not. In this sense, gamma rays, X-rays, microwaves and radio waves are also light. The primary properties of light are intensity, propagation direction, frequency or wavelength spectrum and polarization. Its speed in a vacuum, 299 792 458 metres a second (m/s), is one of the fundamental constants of nature. Like all types of electromagnetic radiation, visible light propagates by massless elementary particles called photons that represents the quanta of electromagnetic field, and can be analyzed as both waves and par ...
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Cis–trans Isomerism
''Cis''–''trans'' isomerism, also known as geometric isomerism or configurational isomerism, is a term used in chemistry that concerns the spatial arrangement of atoms within molecules. The prefixes "''cis''" and "''trans''" are from Latin: "this side of" and "the other side of", respectively. In the context of chemistry, ''cis'' indicates that the functional groups (substituents) are on the same side of some plane, while ''trans'' conveys that they are on opposing (transverse) sides. ''Cis''–''trans'' isomers are stereoisomers, that is, pairs of molecules which have the same formula but whose functional groups are in different orientations in three-dimensional space. ''Cis-trans'' notation does not always correspond to E–Z notation, ''E''–''Z'' isomerism, which is an ''Absolute configuration, absolute'' stereochemical description. In general, ''cis''–''trans'' stereoisomers contain double bonds that do not rotate, or they may contain ring structures, where the rotation ...
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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 (such ...
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