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Cyclopamine
Cyclopamine (11-deoxojervine) is a naturally occurring steroidal alkaloid. It is a teratogenic component of corn lily ('' Veratrum californicum''), which when consumed during gestation has been demonstrated to induce birth defects, including the development of a single eye (cyclopia) in offspring. The molecule was named after this effect, which was originally observed by Idaho lamb farmers in 1957 after their herds gave birth to cycloptic lambs. It then took more than a decade to identify corn lily as the culprit. Later work suggested that differing rain patterns had changed grazing behaviours, which led to a greater quantity of corn lily to be ingested by pregnant sheep. Cyclopamine interrupts the sonic hedgehog signalling pathway, instrumental in early development, ultimately causing birth defects. Discovery and naming In 1957, Idaho sheep ranchers contacted the US Department of Agriculture (USDA) after their sheep gave birth to lambs with a fatal singular eye deformity. Aft ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclopamine In Smoothened Receptor
Cyclopamine (11-deoxojervine) is a naturally occurring steroidal alkaloid. It is a teratogenic component of corn lily (''Veratrum californicum''), which when consumed during gestation has been demonstrated to induce birth defects, including the development of a single eye (cyclopia) in offspring. The molecule was named after this effect, which was originally observed by Idaho lamb farmers in 1957 after their herds gave birth to cycloptic lambs. It then took more than a decade to identify corn lily as the culprit. Later work suggested that differing rain patterns had changed grazing behaviours, which led to a greater quantity of corn lily to be ingested by pregnant sheep. Cyclopamine interrupts the sonic hedgehog signalling pathway, instrumental in early development, ultimately causing birth defects. Discovery and naming In 1957, Idaho sheep ranchers contacted the US Department of Agriculture (USDA) after their sheep gave birth to lambs with a fatal singular eye deformity. After c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and as signal transduction, signaling molecules. Examples include the lipid cholesterol, sex hormones estradiol and testosterone, anabolic steroids, and the anti-inflammatory corticosteroid drug dexamethasone. Hundreds of steroids are found in Fungus, fungi, plants, and animals. All steroids are manufactured in cells from a sterols, sterol: Cholesterol, cholesterol (animals), lanosterol (opisthokonts), or cycloartenol (plants). All three of these molecules are produced via Cyclic compound, cyclization of the triterpene squalene. Structure The steroid nucleus (parent structure, core structure) is called gonane (cyclopentanoperhydrophenanthrene). It is typically composed of seventeen carbon atoms, bonded in fou ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Jervine
Jervine is a steroidal alkaloid with molecular formula C27H39NO3 which is derived from the plant genus ''Veratrum''. Similar to cyclopamine, which also occurs in the genus ''Veratrum'', it is a teratogen implicated in birth defects when consumed by animals during a certain period of their gestation. __TOC__ Physiological effects Jervine is a potent teratogen causing birth defects in vertebrates. In severe cases it can cause cyclopia and holoprosencephaly. Mechanism of action Jervine's biological activity is mediated via its interaction with the 7 pass trans membrane protein smoothened. Jervine binds with and inhibits smoothened, which is an integral part of the hedgehog signaling pathways. With smoothened inhibited, the GLI1 Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells. Function The Gli proteins are the effectors of Hedgehog (Hh) ... t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Veratrum Californicum
''Veratrum californicum'' (California corn lily, white or California false hellebore) is an extremely poisonous plant native to western North America, including the Sierra Nevada and Rocky Mountains, as far north as Washington and as far south as Durango; depending on latitude, it grows from near sea level to as high as 11,000 feet. It grows 1 to 2 meters tall, with an erect, unbranched, heavily leafy stem resembling a cornstalk. It prefers quite moist soil, and can cover large areas in dense stands near streams or in wet meadows. Many inch-wide flowers cluster along the often-branched top of the stout stem; they have 6 white tepals, a green center, 6 stamens, and a 3-branched pistil (see image below). The buds are tight green spheres. The heavily veined, bright green leaves can be more than a foot long. ''Veratrum californicum'' displays mast seeding; populations bloom and seed little in most years, but in occasional years bloom and seed heavily in synchrony. The species usua ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Smoothened
Smoothened is a protein that in humans is encoded by the ''SMO'' gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA). Smoothened (Smo) is a key transmembrane protein that is a key component of the hedgehog signaling pathway, a cell-cell communication system critical for embryonic development and adult tissue homeostasis. Mutations in proteins that relay Hh signals between cells cause birth defects and cancer. The protein that carries the Hh signal across the membrane is the oncoprotein and G-protein coupled receptor (GPCR) Smoothened (Smo). Smo is regulated by a separate transmembrane receptor for Hh ligands called Patched (Ptc). Ptc itself is a tumor suppressor tha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Steroidal Alkaloid
Steroidal alkaloids have the basic steroidal skeleton with nitrogen-based functional groups attached to the skeleton. More specifically, they are distinguished by their tetracyclic cyclopentanoperhydrophenanthrene skeleton that marks their close relationship with sterols. They fall in two major categories: Solanum alkaloids and Veratrum alkaloids. A Steroidal alkaloid has also been found in ''Chonemorpha fragrans'' (Frangipani vine), 'chonemorphine' was used to treat intestinal infections in Wistar rats. (Chatterjee DK et al (1987) Parasitol Res 74, 1, 30-33). Examples Apocynaceae steroid alkaloids The family of apocynaceae alkaloids can be categorized based on their backbone structure, which may include the 5α-pregnane, Δ5-pregnane, or conanine backbone. Typically, these alkaloids feature an amino group or an oxygen compound at the 3rd carbon atom. An illustrative example is latifolinin, which is derived from the conanine backbone. This distinctive structure is charact ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness. The cause of most cases of glioblastoma is not known. Uncommon risk factors include genetic disorders, such as neurofibromatosis and Li–Fraumeni syndrome, and previous radiation therapy. Glioblastomas represent 15% of all brain tumors. They are thought to arise from astrocytes. The diagnosis typically is made by a combination of a CT scan, MRI scan, and tissue biopsy. There is no known method of preventing the cancer. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The medication temozolomide is frequently used a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Multiple Myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, Kidney failure, renal insufficiency, and infections may occur. Complications may include hypercalcemia and amyloidosis. The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, age and certain chemicals. There is an increased risk of multiple myeloma in certain occupations. This is due to the occupational exposure to aromatic hydrocarbon solvents having a role in causation of multiple myeloma. Multiple myeloma is the result of a multi-step malignant transformation, and almost universally originates from the pre-malignant stage monoclonal gammopathy of undetermined significance (MGUS). As MGUS evolves into MM, another pre-stage of the disease is reached, known as Smouldering ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stromal Cell
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term ''stromal'' comes from Latin , "bed covering", and Ancient Greek , , "bed". Stromal cells are an important part of the body's immune response and modulate inflammation through multiple pathways. They also aid in differentiation of hematopoietic cells and forming necessary blood elements. The interaction between stromal cells and tumor cells is known to play a major role in cancer growth and progression. In addition, by regulating local cytokine networks (e.g. M-CSF, LIF), bone marrow stromal cells have been describ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise (especially in older texts). The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, it is also a fundamental step in the transition of tumors from a benign state to a malign ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vismodegib
Vismodegib, sold under the brand name Erivedge, is a medication used for the treatment of basal-cell carcinoma (BCC). The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma . The drug was developed by the biotechnology/pharmaceutical company Genentech. Indication Vismodegib is indicated for people with basal-cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation. Mechanism of action The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactiv ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Functional Analog (chemistry)
In chemistry and pharmacology, functional analogs are chemical compounds that have similar physical, chemical, biochemical, or pharmacological properties. Functional analogs are not necessarily structural analogs with a similar chemical structure. An example of pharmacological functional analogs are morphine, heroin and fentanyl, which have the same mechanism of action, but fentanyl is structurally quite different from the other two with significant variance in dosage. File:Morphin - Morphine.svg, Morphine File:Heroin - Heroine.svg, Heroin File:Fentanyl2DCSD.svg, Fentanyl Fentanyl is a highly potent synthetic piperidine opioid primarily used as an analgesic (pain medication). It is 30 to 50 times more Potency (pharmacology), potent than heroin and 50 to 100 times more potent than morphine. Its primary Medici ... See also * Federal Analogue Act References Chemical nomenclature Pharmacology {{pharma-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
