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Nirogacestat
Nirogacestat, sold under the brand name Ogsiveo, is an anti-cancer medication used for the treatment of desmoid tumors. It is a selective gamma secretase enzyme inhibitor, inhibitor that is taken by mouth. Nirogacestat was approved for medical use in the United States in November 2023. It is the first medication approved by the US Food and Drug Administration (FDA) for the treatment of desmoid tumors. The FDA considers it to be a first-in-class medication. European Medicines Agency (EMA) considers it an orphan drug. and issued a positive opinion on its approval Medical uses Nirogacestat is indicated for adults with progressing desmoid tumors who require systemic treatment. Adverse effects Nirogacestat treatment has been associated with several notable adverse effects across multiple studies. Hypophosphatemia is a significant and common side effect, with an incidence exceeding 40% in patients with various cancers including desmoid tumors, sarcoma, metastatic breast can ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Desmoid Tumors
Aggressive fibromatosis or desmoid tumor is a rare condition. Desmoid tumors are a type of fibromatosis and related to sarcoma, though without the ability to spread throughout the body (metastasize). The tumors arise from cells called fibroblasts, which are found throughout the body and provide structural support, protection to the vital organs, and play a critical role in wound healing. These tumors tend to occur in women in their thirties, but can occur in anyone at any age. They can be either relatively slow-growing or malignant. However, aggressive fibromatosis is locally aggressive and invasive, with spindle-like growths. The tumors can lead to pain, life-threatening problems, or, rarely, death when they invade other soft tissue or compress vital organs such as intestines, kidneys, lungs, blood vessels, or nerves. Most cases are sporadic, but some are associated with familial adenomatous polyposis (FAP). Approximately 10% of individuals with Gardner's syndrome, a type of FA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
By Mouth
Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administration can be easier and less painful than other routes of administration, such as Injection (medicine), 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 able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth". The expression is used in medicine to describe a treatment that is taken orally (but not ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cmax (pharmacology)
is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose. It is a standard measurement in pharmacokinetics. Description is the opposite of , which is the minimum (or trough) concentration that a drug achieves after dosing. The related pharmacokinetic parameter is the time at which the is observed. After an intravenous administration, and are closely dependent on the experimental protocol, since the concentrations are always decreasing after the dose. But after oral administration, and are dependent on the extent, and the rate of drug absorption and the disposition profile of the drug. They could be used to characterize the properties of different formulations in the same subject. Short term drug side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Steady State (biochemistry)
In biochemistry, steady state refers to the maintenance of constant internal concentrations of Biomolecule, molecules and ions in the Cell (biology), cells and Organ (biology), organs of living systems. Living organisms remain at a dynamic steady state where their internal composition at both cellular and gross levels are relatively constant, but different from Equilibrium chemistry, equilibrium concentrations. A continuous flux of mass and energy results in the constant Anabolism, synthesis and Catabolism, breakdown of molecules via chemical reactions of biochemical pathways. Essentially, steady state can be thought of as homeostasis at a cellular level. Maintenance of steady state Metabolic regulation achieves a balance between the rate of input of a substrate and the rate that it is degraded or converted, and thus maintains steady state. The rate of metabolic flow, or flux, is variable and subject to metabolic demands. However, in a metabolic pathway, steady state is main ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hydrogen Bonds
In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, covalently bonded to a more electronegative donor atom or group (Dn), interacts with another electronegative atom bearing a lone pair of electrons—the hydrogen bond acceptor (Ac). Unlike simple dipole–dipole interactions, hydrogen bonding arises from charge transfer (nB → σ*AH), orbital interactions, and quantum mechanical delocalization, making it a resonance-assisted interaction rather than a mere electrostatic attraction. The general notation for hydrogen bonding is Dn−H···Ac, where the solid line represents a polar covalent bond, and the dotted or dashed line indicates the hydrogen bond. The most frequent donor and acceptor atoms are nitrogen (N), oxygen (O), and fluorine (F), due to their high electronegativity and ability to engage in stronger ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Presenilin-1
Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the ''PSEN1'' gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease. Structure Presenilin possesses a 9 transmembrane domain topology, with an extracellular C-terminus and a cytosolic N-terminus. Presenilin undergoes endo-proteolytic processing to produce ~27-28 kDa N-terminal and ~16-17 kDa C-terminal fragments in humans. Furthermore, presenilin exists in the cell mainly as a heterodimer of the C-terminal and N-terminus fragments. When presenilin 1 is overexpressed, the full length protein accumulates in an inactive form. Based on evidence that a gamma-secretase inhibitor binds to the fragments, the cleaved presenilin complex is considered to be the active form. Function ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cryogenic Electron Microscopy
Cryogenic electron microscopy (cryo-EM) is a transmission electron microscopy technique applied to samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid ethane or a mixture of liquid ethane and propane. While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution. This has attracted wide attention to the approach as an alternative to X-ray crystallography or NMR spectroscopy in the structural biology field. In 2017, the Nobel Prize in Chemistry was awarded to Jacques Dubochet, Joachim Frank, and Richard Henderson "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution." '' Nature Methods'' also named cryo- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Notch 4
Neurogenic locus notch homolog 4 (Notch 4) is a protein that in humans is encoded by the ''NOTCH4'' gene located on chromosome 6. Gene An alternative splice variant of the NOTCH4 gene has been described, but its biological significance has not been determined. Structure The neurogenic locus notch homolog 4 protein is a member of the Notch family. Members of this type 1 transmembrane protein family share structural characteristics. These include an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain that consists of multiple, but different, domain types. Function Notch protein family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling pathway is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells In Drosophila, ''notch'' interacts with its cell-bound ligands (delta and serrate) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NOTCH3
Neurogenic locus notch homolog protein 3 (Notch 3) is a protein that in humans is encoded by the ''NOTCH3'' gene. Function This gene encodes the third discovered human homologue of the ''Drosophila melanogaster'' type I membrane protein notch. In ''Drosophila'', notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Pathology Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mutations in NOTCH3 have also been identified in families with Alzheimer's disease. Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
