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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] |
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] |
Holoprosencephaly Induced By Cyclopamine
Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres, typically occurring between the 18th and 28th day of gestation. Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy. The condition also occurs in other species. Holoprosencephaly is estimated to occur in approximately 1 in every 250 conceptions; most cases are not compatible with life and result in fetal death in utero due to deformities to the skull and brain. However, holoprosencephaly is still estimated to occur in approximately 1 in every 8,000 live births. When the embryo's forebrain does not divide to form bilateral cerebral hemispheres (the left and right halves of the brain), it causes defects in the development of the face and in brain structure and function. The severity of holoprosencephaly is highly variable. In less severe cases, babies are born with normal or nea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Semisynthetic
Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with distinct chemical and medicinal properties. The novel compounds generally have a high molecular weight or a complex molecular structure, more so than those produced by total synthesis from simple starting materials. Semisynthesis is a means of preparing many medicines more cheaply than by total synthesis since fewer chemical steps are necessary. Drugs derived from natural sources are commonly produced either by isolation from their natural source or, as described here, through semisynthesis of an isolated agent. From the perspective of chemical synthesis, living organisms act as highly efficient chemical factories, capable of producing structurally complex compounds through biosynthesis. In contrast, engineered chemical synthesis, alth ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Saridegib
Saridegib, also known as IPI-926, is an experimental drug candidate undergoing clinical trials for the treatment of various types of cancer, including hard-to-treat hematologic malignancies such as myelofibrosis and ligand-dependent tumors such as chondrosarcoma. IPI-926 exhibits its pharmacological effect by inhibition of the G protein-coupled receptor smoothened, a component of the hedgehog signaling pathway. Chemically, it is a semi-synthetic derivative of the alkaloid cyclopamine. The process begins with cyclopamine extracted from harvested Veratrum californicum which is taken through a series of alterations resulting in an analogue of the natural product cyclopamine, making IPI-926 the only compound in development/testing that is not fully synthetic. Saridegib is a member of a class of anti-cancer compounds known as hedgehog pathway inhibitors Hedgehog pathway inhibitors, also sometimes called hedgehog inhibitors, are small molecules that inhibit the activity of a compone ... [...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] |
Sonidegib
Sonidegib (INN), sold under the brand name Odomzo, is a medication used to treat cancer. Sonidegib is a Hedgehog signaling pathway inhibitor (via smoothened antagonism). Approvals and indications It was approved for medical use in the United States and in the European Union in 2015 It is indicated for the treatment of adults with locally advanced basal-cell carcinoma that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. Pharmacology Sonidegib is administered by mouth. Common side effects include muscle spasms, hair loss, fatigue, abdominal pain, nausea, headache, and weight loss. Sonidegib binds to and inhibits smoothened to inhibit activation of the Hedgehog pathway. Sonidegib is primarily metabolized by CYP3A and is eliminated hepatically. Development It has been investigated as a potential treatment for: * Pancreatic cancer * Breast cancer * Basal cell carcinoma of the skin * Small cell lung cancer * ... [...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] |
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] |
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] |
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] |
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] |
