|
AP26113
Brigatinib, sold under the brand name Alunbrig among others, is a small-molecule targeted cancer therapy being developed by Ariad Pharmaceuticals, Inc. Brigatinib acts as both an anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) inhibitor. Brigatinib could overcome resistance to osimertinib conferred by the EGFR C797S mutation if it is combined with an anti-EGFR antibody such as cetuximab or panitumumab. Mechanism of action Brigatinib is an inhibitor of ALK and mutated EGFR. ALK was first identified as a chromosomal rearrangement in anaplastic large cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as ALCL. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy. Brigatinib inhibits ROS proto-oncogene-1 fusions and EGFR mutations and has a remarkab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epidermal Growth Factor Receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer. Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Cohen shared the 1986 Nobel Prize in Medicine with Rita Levi-Montalcini for their discovery of growth factors. Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as Alzheimer's, while over-expression is associated with the development of a wide variety of tumors. Interruption of EGFR signalling, either by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epidermal Growth Factor Receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer. Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Cohen shared the 1986 Nobel Prize in Medicine with Rita Levi-Montalcini for their discovery of growth factors. Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as Alzheimer's, while over-expression is associated with the development of a wide variety of tumors. Interruption of EGFR signalling, either by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
EGFR Inhibitor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer. Epidermal growth factor and its receptor was discovered by Stanley Cohen of Vanderbilt University. Cohen shared the 1986 Nobel Prize in Medicine with Rita Levi-Montalcini for their discovery of growth factors. Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as Alzheimer's, while over-expression is associated with the development of a wide variety of tumors. Interruption of EGFR signalling, either b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T790M
T790M, also known as Thr790Met, is a gatekeeper mutation of the epidermal growth factor receptor (EGFR). The mutation substitutes a threonine (T) with a methionine (M) at position 790 of exon 20, affecting the ATP binding pocket of the EGFR kinase domain. Threonine is a small polar amino acid; methionine is a larger nonpolar amino acid. Rather than directly blocking inhibitor binding to the active site, T790M increases the affinity for ATP so that the inhibitors are outcompeted; covalent inhibitors such as neratinib can overcome this resistance. Clinical Over 50% of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) is caused by a mutation in the ATP binding pocket of the EGFR kinase domain involving substitution of a small polar threonine residue with a large nonpolar methionine residue, T790M. In November 2015, the US FDA granted accelerated approval to osimertinib (Tagrisso) for the treatment of patients with metastatic epidermal growth factor receptor (EGF ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Receptor Tyrosine Kinase Inhibitors , a device for the reception of electromagnetic signals ...
Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a neurotransmitter, or other substance **Cell surface receptor, a receptor on the outer surface of a cell membrane, that takes part in communication between the cell and the outside world **Nuclear receptor, a receptor found within cells that is responsible for sensing steroid and thyroid hormones and certain other molecules **Immune receptor, a receptor that occurs on the surface of immunocytes and binds to antigens *Receiver (radio) In radio communications, a radio receiver, also known as a receiver, a wireless, or simply a radio, is an electronic device that receives radio waves and converts the information carried by them to a usable form. It is used with an antenna. T ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Piperidines
Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor described as objectionable, and typical of amines. The name comes from the genus name ''Piper'', which is the Latin word for pepper. Although piperidine is a common organic compound, it is best known as a representative structure element within many pharmaceuticals and alkaloids, such as natural-occurring solenopsins. Production Piperidine was first reported in 1850 by the Scottish chemist Thomas Anderson and again, independently, in 1852 by the French chemist Auguste Cahours, who named it. Both of them obtained piperidine by reacting piperine with nitric acid. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst: : C5H5N + 3 H2 → C5H10NH Pyridine can also be reduce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Organophosphine Oxides
Organophosphines are organophosphorus compounds with the formula PR''n''H3−''n'', where R is an organic substituent. These compounds can be classified according to the value of ''n'': primary phosphines (''n'' = 1), secondary phosphines (''n'' = 2), tertiary phosphines (''n'' = 3). All adopt pyramidal structures. Organophosphines are generally colorless, lipophilic liquids or solids. The parent of the organophosphines is phosphine (PH3). Annette Schier and Hubert Schmidbaur"P-Donor Ligands" in Encyclopedia of Inorganic Chemistry 2006, Wiley-VCH, Weinheim. 1° vs 2° vs 3° phosphines Organophophines are classified according to the number of organic substituents. Primary phosphines Primary (1°) phosphines, with the formula RPH2, are typically prepared by alkylation of phosphine. Simple alkyl derivatives such as methylphosphine (CH3PH2) are prepared by alkylation of alkali metal derivatives MPH2 (M is Li, Na, or K). Another synthetic route in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP3A4 Inducers
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme. While many drugs are deactivated by CYP3A4, there are also some drugs which are ''activated'' by the enzyme. Some substances, such as some drugs and furanocoumarins present in grapefruit juice, interfere with the action of CYP3A4. These substances will therefore either amplify or weaken the action of those drugs that are modified by CYP3A4. CYP3A4 is a member of the cytochrome P450 family of oxidizing enzymes. Several other members of this family are also involved in drug metabolism, but CYP3A4 is the most common and the most versatile one. Like all members of this family, it is a hemoprotein, i.e. a protein containing a heme group with an iron atom. In humans, t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cancer Treatments
Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. chemotherapy before surgery). The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). Cancer genome sequencing helps in determining which cancer the patient exactly has for determining the best therapy for the cancer. A number of experimental cancer treatments are also under development. Under current estimates, two in five people will have cancer at some point in their lifetime. Complete removal of the cancer without damage to the rest of the body (that is, achieving cure with near-zero adverse effects) is the ideal, if rarely achieved, goal of treatment and is often the goal in practice. Sometimes this can be accomplished by sur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, Prescription drug, prescription and Over-the-counter drug, over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, Animal feed, animal foods & feed and Veterinary medicine, veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), but the agency also enforces other laws, notably Section 361 of the Public Health Service Act, as well as associated regulations. Much of this regulatory-enforcement work is not d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
.jpg "Click for more on -> Food And Drug Administration")