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Glycine Transporter 1
Sodium- and chloride-dependent glycine transporter 1, also known as glycine transporter 1, is a protein that in humans is encoded by the ''SLC6A9'' gene which is promising therapeutic target for treatment of diabetes and obesity. Selective inhibitors Elevation of extracellular synaptic glycine concentration by blockade of GlyT1 has been hypothesized to potentiate NMDA receptor function in vivo and to represent a rational approach for the treatment of schizophrenia and cognitive disorders. Several drug candidates have reached clinical trials. * ASP2535 * Bitopertin (RG1678), which has entered phase II trials for the treatment of schizophrenia * Iclepertin ( BI 425809) by Boehringer Ingelheim which is thought to improve cognitive impairment due to schizophrenia * Org 25935 (Sch 900435) * PF-03463275 (in phase II trial) * Pesampator (PF-04958242) by Pfizer * Sarcosine which is thought to improve cognitive impairment due to schizophrenia Pathological mutations Mutations of the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of Gene product, RNA or protein from a gene), DNA is first transcription (biology), copied into RNA. RNA can be non-coding RNA, directly functional or be the intermediate protein biosynthesis, template for the synthesis of a protein. The transmission of genes to an organism's offspring, is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype, that is specific to every given individual, within the gene pool of the population (biology), population of a given species. The genotype, along with environmental and developmental factors, ultimately determines the phenotype ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine disrupts the formation of alpha-helices in secondary protein structure. Its small side chain causes it to favor random coils instead. Glycine is also an inhibitory neurotransmitter – interference with its release within the spinal cord (such as during a '' Clostridium tetani'' infection) can cause spastic paralysis due to uninhibited muscle contraction. It is the only achiral proteinogenic amino acid. It can fit into both hydrophilic and hydrophobic environments, due to its minimal side chain of only one hydrogen atom. History and etymology Glycine was discovered in 1820 by French chemist Henri Braconnot when he hydrolyzed gelatin by boiling it with sulfuric acid. He originally called it "sugar of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NMDA Receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA receptor, AMPA and kainate receptors. Depending on its subunit composition, its Ligand (biochemistry), ligands are Glutamate (neurotransmitter), glutamate and glycine (or D-Serine, D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Magnesium, Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a "coincidence detector" and only once both of these conditions are met, the channel opens and it allows cation, positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions. The N ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Schizophrenia
Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, flat or inappropriate affect. Symptoms Prodrome, develop gradually and typically begin during young adulthood and rarely resolve. There is no objective diagnostic test; diagnosis is based on observed behavior, a psychiatric history that includes the person's reported experiences, and reports of others familiar with the person. For a diagnosis of schizophrenia, the described symptoms need to have been present for at least six months (according to the DSM-5) or one month (according to the ICD-11). Many people with schizophrenia have other mental disorders, especially mood disorder, mood, anxiety disorder, anxiety, and substance use disorders, substance use disorders, as well as obsessive–compulsive disorder (OCD). About 0.3% to 0.7% of peo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ASP2535
ASP2535 is an inhibitor of the type 1 glycine transporter. It could potentially be used in treatment of Alzheimer's disease and schizophrenia. Potential uses ASP2535 has been investigated for the treatment of Alzheimer's disease and schizophrenia, it is able to inhibit the memory deficit induced by scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ..., an anticholinergic agent. References {{Receptor-stub Disubstituted pyridines Benzoxadiazoles Triazoles Isopropyl compounds Phenyl compounds ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bitopertin
Bitopertin (developmental code names RG1678; RO-4917838) is a glycine reuptake inhibitor which was under development by Roche as an adjunct to antipsychotics for the treatment of persistent negative symptoms or suboptimally controlled positive symptoms associated with schizophrenia. Research into this indication has been largely halted as a result of disappointing trial results. As of 2024, it is under development for the management of erythropoietic protoporphyria. Bitopertin is a glycine transporter 1 (GlyT1) inhibitor that increases levels of the neurotransmitter glycine by inhibiting its reuptake from the synaptic cleft. Glycine acts as a required co-agonist along with glutamate at ''N''-methyl-D-aspartate (NMDA) receptors. Erythropoietic protoporphyria Glycine is an early and crucial substrate in the biosynthesis of haem; inhibiting its transport by blocking GlyT1 reduces its availability for haem biosynthesis and this reduces the downstream accumulation of protoporp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, pharmaceutical drug, drugs, medical nutrition therapy, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received institutional review board, health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small Pilot experiment, pi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BI 425809
Iclepertin (developmental code name BI 425809) is an investigational nootropic to enhance the cognition and functional capacity in schizophrenia developed by Boehringer Ingelheim. As of May 2020, it is in phase III of clinical trial under the code name CONNEX-3. BI 425809 is an inhibitor of glycine transporter 1 (Gly-T1) that in phase II improved cognition after 12 weeks in patients with schizophrenia. Doses of 10 mg and 25 mg showed the largest separation from placebo. If these encouraging results are confirmed in phase 3 trials, BI 425809 could provide an effective treatment for cognitive impairment associated with schizophrenia. Schizophrenia is characterized by abnormalities in glutamatergic pathways related to NMDA receptor hypofunction. Inhibition of GlyT1 on the presynaptic membrane or astrocytes is hypothesized to increase glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Org 25935
ORG-25935, also known as SCH-900435 is a synthetic drug developed by Organon International, which acts as a selective inhibitor of the glycine transporter GlyT-1. In animal tests it reduces alcohol consumption and has analgesic and anticonvulsant effects, but it has mainly been studied for its antipsychotic properties, and in human trials it was shown to effectively counteract the effects of the dissociative drug ketamine. See also * Glycine reuptake inhibitor A glycine reuptake inhibitor (GRI) is a type of drug which inhibits the reuptake of the neurotransmitter glycine by blocking one or more of the glycine transporters (GlyTs). Examples of GRIs include bitopertin (RG1678), iclepertin (BI-425809), ... References Alpha-Amino acids Drugs acting on the nervous system Glycine reuptake inhibitors {{nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pesampator
Pesampator (; developmental code names BIIB-104 and PF-04958242) is a positive allosteric modulator (PAM) of the AMPA receptor (AMPAR), an ionotropic glutamate receptor, which was under development by Pfizer for the treatment of cognitive symptoms in schizophrenia. In March 2018, the development of the drug was transferred over from Pfizer to Biogen. It was also under development for the treatment of age-related sensorineural hearing loss, but development for this indication was terminated due to insufficient effectiveness. In July 2022, Biogen discontinued the development of pesampator for cognitive symptoms in schizophrenia due to ineffectiveness. Pesampator belongs to the biarylpropylsulfonamide group of AMPAR PAMs, which also includes LY-404187, LY-503430, and mibampator (LY-451395) among others. It is described as a "high-impact" AMPAR PAM, unlike so-called "low-impact" AMPAR PAMs like CX-516 and its congener farampator (CX-691, ORG-24448). In animals, low doses of pesampa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sarcosine
Sarcosine, also known as ''N''-methylglycine, or monomethylglycine, is a amino acid with the formula CH3N(H)CH2CO2H. It exists at neutral pH as the zwitterion CH3N+(H)2CH2CO2−, which can be obtained as a white, water-soluble powder. Like some amino acids, sarcosine converts to a cation at low pH and an anion at high pH, with the respective formulas CH3N+(H)2CH2CO2H and CH3N(H)CH2CO2−. Sarcosine is a close relative of glycine, with a secondary amine in place of the primary amine. Sarcosine is ubiquitous in biological materials. It is used in manufacturing biodegradable surfactants and toothpastes as well as in other applications. It is also a reagent in organic synthesis. Sarcosine is sweet to the taste. Biochemistry Sarcosine is an intermediate and byproduct in glycine synthesis and degradation. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase, while Glycine N-methyltransferase, glycine-''N''-methyl transferase generates sarcosine from glycine. S ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
