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Lestaurtinib
Lestaurtinib ( rINN, codenamed CEP-701) is a tyrosine kinase inhibitor structurally related to staurosporine. This semisynthetic derivative of the indolocarbazole K252a was investigated by Cephalon as a treatment for various types of cancer. It is an inhibitor of the kinases fms-like tyrosine kinase 3 (FLT3), Janus kinase 2 ( JAK2), tropomyosin receptor kinase (''trk'') A (TrkA), TrkB and TrkC. Uses Lestaurtinib has undergone clinical trials for the treatment of various cancers, including pancreatic and prostate cancers, V617F JAK2 positive polycythemia vera and essential thrombocytosis, and refractory neuroblastoma. The most significant effort was invested in developing lestaurtinib for the treatment of acute myelogenous leukemia (AML). 24% of the adult AML-affected population exhibits FLT3 mutations, which are associated with an increased likelihood of relapse and mortality after treatment above the general AML population. FLT3 mutations suppress apoptosis in mutated cells ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Janus Kinase Inhibitor
A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes ( JAK1, JAK2, JAK3, TYK2), thereby interfering with the JAK-STAT signaling pathway in lymphocytes. It is used in the treatment of cancer and inflammatory diseases such as rheumatoid arthritis and various skin conditions.A Janus kinase 3 inhibitor is attractive as a possible treatment of various autoimmune diseases since its function is mainly restricted to lymphocytes. As of 2017, development of a selective JAK3 inhibitor was ongoing. Contraindications The US Food and Drug Administration (FDA) requires the boxed warning for tofacitinib, baricitinib, and upadacitinib to include information about the risks of serious heart-related events, cancer, blood clots, and death. The Pharmacovigilance Risk Assessment Committee of the European Medicines Agency (EMA) recommends that the Janus kinase ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
K252a
K252a is an alkaloid isolated from '' Nocardiopsis'' bacteria. This staurosporine analog is a highly potent cell permeable inhibitor of CaM kinase and phosphorylase kinase (IC50 = 1.8 and 1.7 nmol/ L, respectively). At higher concentrations it is also an efficient inhibitor of serine/threonine protein kinases (IC50 of 10 to 30 nmol/L).Tapley, P. ''et al.'' (1992) Oncogene 7, 371. K252a is reported to promote myogenic differentiation in C2 mouse myoblasts and has been shown to block the neuronal differentiation of rat pheochromocytoma PC12 cells by inhibition of trk tyrosine kinase activity. K252a has been reported in preclinical research as a potential treatment for psoriasisPromising New Treatments for Psoriasis, Sarah Dubois Declercq and Roxane Pouliot >.The Scientific World Journal; Volume 2013, Article ID 980419; https://dx.doi.org/10.1155/2013/980419 K252a inhibits tyrosine phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molec ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FLT3
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the ''FLT3'' gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L). It is expressed on the surface of many hematopoietic progenitor cells. Signalling of FLT3 is important for the normal development of haematopoietic stem cells and progenitor cells. The FLT3 gene is one of the most frequently mutated genes in acute myeloid leukemia (AML). High levels of wild-type FLT3 have been reported for blast cells of some AML patients without FLT3 mutations. These high levels may be associated with worse prognosis. Structure FLT3 is composed of five extracellular immunoglobulin-like domains, an extracellular domain, a transmembrane domain, a juxtamembrane domain and a tyrosine-kinase ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Quizartinib
Quizartinib (AC220) is a small molecule receptor tyrosine kinase inhibitor, originally from Ambit Biosciences and later acquired by Daiichi Sankyo, that is currently under development for the treatment of acute myeloid leukaemia. Quizartinib is sold under the brand name Vanflyta in Japan. Its molecular target is FLT3, also known as CD135 which is a proto-oncogene. Flt3 mutations are among the most common mutations in acute myeloid leukaemia due to internal tandem duplication of Flt3. The presence of this mutation is a marker of adverse outcome. __TOC__ Mechanism Specifically, quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/ FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFR Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Midostaurin
Midostaurin, sold under the brand name Rydapt & Tauritmo both by Novartis, is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium ''Streptomyces staurosporeus''. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. AML and MDS Midostaurin was found to be active against oncogenic CD135 (FMS-like tyrosine kinase 3 receptor, FLT3), in preclinical studies. Clinical trials have primarily focused on relapsed/refractory AML and MDS and have included single agent and combination agent studies. After successful Phase II clinical trials, midostaurin was found to prolong survival of FLT3-mutated AML patients when combined with conventional induction and consolidation therapies in a randomized Phase III clinical trial. On April 28, 20 ... [...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] |
Teva Pharmaceutical Industries
Teva Pharmaceutical Industries Ltd. (also known as Teva Pharmaceuticals) is an Israeli multinational pharmaceutical company with headquarters in Tel Aviv, Israel. It specializes primarily in generic drugs, but other business interests include active pharmaceutical ingredients and, to a lesser extent, proprietary pharmaceuticals. Teva Pharmaceuticals was the largest generic drug manufacturer, when it was surpassed briefly by US-based Pfizer. Teva regained its market leader position once Pfizer spun off its generic drug division in a merger with Mylan, forming the new company Viatris at the end of 2020. Overall, Teva is the 18th largest pharmaceutical company in the world. Teva's facilities are located in Israel, North America, Europe, Australia, and South America. Teva shares are listed on the Tel Aviv Stock Exchange. The company is a member of the Pharmaceutical Research and Manufacturers of America (PhRMA). History Salomon, Levin, and Elstein Teva's earliest predecessor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orphan Drug
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy in many countries and has yielded medical breakthroughs that might not otherwise have been achieved, due to the economics of drug research and development. In the U.S. and the EU, it is easier to gain marketing approval for an orphan drug. There may be other financial incentives, such as an extended period of exclusivity, during which the producer has sole rights to market the drug. All are intended to encourage development of drugs which would otherwise lack sufficient profit motive to attract corporate research budgets and personnel. Definition According to the US Food and Drug Administration (FDA), an orphan drug is defined as one "intended for ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
