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Temsirolimus
Temsirolimus, sold under the brand name Torisel, is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in May 2007, and was also approved by the European Medicines Agency (EMA) in November 2007. It is a derivative and prodrug of sirolimus. Mechanism of action Temsirolimus is a specific inhibitor of mTOR and interferes with the synthesis of proteins that regulate proliferation, growth, and survival of tumor cells. Though temsirolimus shows activity on its own, it is also known to be converted to sirolimus (rapamycin) in vivo; therefore, its activity may be more attributed to its metabolite rather than the prodrug itself (despite claims to the contrary by the manufacturer). Treatment with temsirolimus leads to cell cycle arrest in the G1 phase, and also inhibits tumor angiogenesis by reducing synthesis of VEGF. mTOR (mammalian target of rapamycin) is a kinase ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Discovery And Development Of MTOR Inhibitors
mTOR inhibitors are a drug class, class of drugs used to treat several human diseases, including cancer, autoimmune diseases, and neurodegeneration. They function by inhibiting the mammalian target of rapamycin (mTOR) (also known as the mechanistic target of rapamycin), which is a serine/threonine-specific protein kinase that belongs to the family of Phosphoinositide 3-kinase, phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs (rapamycin and its analogs), which have shown tumor responses in clinical trials against various tumor types. History The discovery of mTOR was made in 1994 while investigating the mechanism of action of its enzyme inhibitor, inhibitor, rapamycin. Rapamycin was first discovered in 1975 in a soil sample from Easter Island of Oceania, South Pacific, also k ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sirolimus
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumour (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mammalian target of rapamycin (mTOR) kinase inhibitor that reduces the sensitivity of T cells and B cells to interleukin-2 (IL-2), inhibiting their activity. This compound also has a use in cardiovascular drug-eluting stent technologies to inhibit restenosis. It is produced by the bacterium '' Streptomyces hygroscopicus'' and was isolated for the first time in 1972, from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially deve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Renal Cell Carcinoma
Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the Proximal tubule, proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, responsible for approximately 90–95% of cases. It is more common in men (with a male-to-female ratio of up to 2:1). It is most commonly diagnosed in the elderly (especially in people over 75 years of age). Initial treatment is most commonly either partial or complete removal of the affected kidney(s). Where the cancer has not metastasised (spread to other organs) or burrowed deeper into the tissues of the kidney, the five-year survival rate is 65–90%, but this is lowered considerably when the cancer has spread. The body is remarkably good at hiding the symptoms and as a result people with RCC often have advanced disease by the time it is discovered. The initial symptoms of RCC often include haematuria, blood in the urine ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mammalian Target Of Rapamycin
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTORC1, mTOR complex 1 and mTORC2, mTOR complex 2, which regulate different cellular processes. In particular, as a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and Transcription (genetics), transcription. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. mTORC2 has also ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sorafenib
Sorafenib, sold under the brand name Nexavar, is a kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma), advanced primary liver cancer (hepatocellular carcinoma), FLT3-ITD positive AML and radioactive iodine resistant advanced thyroid carcinoma. Mechanism of action Sorafenib is a protein kinase inhibitor with activity against many protein kinases, including VEGFR, PDGFR and RAF kinases. Of the RAF kinases, sorafenib is more selective for c-Raf than B-RAF. (See BRAF (gene)#Sorafenib for details the drug's interaction with B-Raf.) Sorafenib treatment induces autophagy, which may suppress tumor growth. Based on its 1,3-disubstituted urea structure, sorafenib is also a potent soluble epoxide hydrolase inhibitor and this activity likely reduces the severity of its adverse effects. Medical uses Sorafenib is indicated as a treatment for advanced renal cell carcinoma (RCC), unresectable hepatocellular carcinomas (HCC) and thy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Wyeth
Wyeth Pharmaceuticals Inc. was a pharmaceutical company until it was purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania, in 1860 as John Wyeth and Brother. Its headquarters moved to Collegeville, Pennsylvania, and Madison, New Jersey, before its headquarters were consolidated with Pfizer's in New York City after the 2009 merger. Wyeth manufactured over-the-counter drug, over-the-counter (OTC) drugs Robitussin and the analgesic Advil (ibuprofen) as well as prescription drugs Premarin and Effexor. History 1860–1899 In 1860, pharmacists John (1834–1907) and Frank Wyeth opened a drugstore with a small research lab on Walnut Street in Philadelphia. In 1862, on the suggestion of doctors, they began to manufacture large quantities of commonly ordered medicines. They were successful, and in 1864 they began supplying medicines and Meat extract, beef extract to the Union army during the American Civil War, Civil War. In 1872, Henry Bower, a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumor Suppressor Gene
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The Loss-of-function mutation, loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes. TSGs can be grouped into the following categories: caretaker genes, gatekeeper genes, and more recently landscaper genes. Caretaker genes ensure stability of the genome via DNA repair and subsequently when mutated allow mutations to accumulate. Meanwhile, gatekeeper genes directly regulate cell growth by either inhibiting cell cycle progression or inducing apoptosis. Lastly, landscaper genes regulate growth by contributing to the surrounding e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Malignant
Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malignancy is not self-limited in its growth, is capable of invading into adjacent tissues, and may be capable of spreading to distant tissues. A benign tumor has none of those properties, but may still be harmful to health. The term benign in more general medical use characterizes a condition or growth that is not cancerous, i.e. does not spread to other parts of the body or invade nearby tissue. Sometimes the term is used to suggest that a condition is not dangerous or serious. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis. Malignant tumors are also characterized by genome instability, so that cancers, as assessed by whole genome sequencing, frequently have between 10,000 and 100,000 mutations in their ent ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Renal Cancer
Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, a lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include spread to the lungs or brain. The main types of kidney cancer are renal cell cancer (RCC), transitional cell cancer (TCC), and Wilms' tumor. RCC makes up approximately 80% of kidney cancers, and TCC accounts for most of the rest. Risk factors for RCC and TCC include smoking, certain pain medications, previous bladder cancer, being overweight, high blood pressure, certain chemicals, and a family history. Risk factors for Wilms' tumor include a family history and certain genetic disorders such as WAGR syndrome. Diagnosis may be suspected based on symptoms, urine testing, and medical imaging. It is confirmed by tissue biopsy. Treatment may include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy. Kidney c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sunitinib
Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications. As of August 2021, sunitinib is available as a generic medicine in the US. Medical uses Gastrointestinal stromal tumor Like renal cell carcinoma, gastrointestinal stromal tumors do not generally respond to standard chemotherapy or radiation. Imatinib was the first chemotherapeutic agent proven effective for metastatic gastrointestinal stromal tumors and represented a significant development in the treatment of this rare but challenging disease. However, approximately 20% of patients do not respond to imatinib (early or primary resistance), and among those who do respond init ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and innate lymphoid cells (ILCs; "innate T cell-like" cells involved in mucosal immunity and homeostasis), of which natural killer cells are an important subtype (which functions in cell-mediated, cytotoxic innate immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte" (with ''cyte'' meaning cell). Lymphocytes make up between 18% and 42% of circulating white blood cells. Types The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. They can also be classified as small lymphocytes and large lymphocytes based on their size and appearance. Lymphocytes can be identified by their large nucleus. T cells and B cells T cells (thymus cells) and B cells ( bone marrow- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
