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TAK-994
TAK-994 is an orexin receptor agonist which is under development by Takeda for the treatment of narcolepsy. It is a small-molecule and orally active compound and acts as a highly selective agonist of the orexin receptor 2 (OX2) (>700-fold selectivity over the orexin receptor 1 (OX1)). TAK-994 is related to danavorexton (TAK-925). The compound reached phase 2 clinical trials for narcolepsy. However, clinical development was discontinued in October 2021 for safety reasons. The chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of a ... of TAK-994 has yet to be disclosed. See also * Orexin receptor § Agonists * List of investigational sleep drugs § Orexin receptor agonists References Experimental drugs Orexin receptor agonists {{Nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orexin Receptor 2
Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene. Structure The structure of the receptor has been solved to 2.5 Å resolution as a fusion protein bound to suvorexant using lipid-mediated crystallization. Function OX2 is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with OX1. OX2 binds both orexin A and orexin B neuropeptides. OX2 is involved in the central feedback mechanism that regulates feeding behaviour. Mice with enhanced OX2 signaling are resistant to high-fat diet-induced obesity. This receptor is activated by Hipocretin, which is a wake-promoting hypothalamic neuropeptide that acts as a critical regulator of sleep in animals as Zebrafish or Mammals. This protein has mutations in Astyanax mexicanus that reduces the sleep needs of the cavefish. Ligands Agonists * Danavorexton (TAK-925) – selective OX2 receptor agonist * Fi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orexin Receptor Agonist
The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (, ). Both orexin receptors exhibit a similar pharmacology – the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 5- to 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors. Several orexin receptor antagonists are in development for potential use in sleep disorders. The first of these, suvorexant, has been on the market in the United States since 2015. There were two orexin agonists under development . Ligands Several drugs acting on the orexin system are under development, either orexin agonists for the treatment of conditions such as narcolepsy, or orexin antagonists for insomnia. In August 2015 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
List Of Investigational Sleep Drugs
This is a list of investigational sleep drugs, or drugs for the treatment of sleep disorders that are currently under development for clinical use but are not yet approved. ''Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.'' Insomnia GABAA receptor potentiators * EVT-201 – GABAA receptor positive allosteric modulator * (GF-015535-00) – GABAA receptor positive allosteric modulato [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orexin Receptor
The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (, ). Both orexin receptors exhibit a similar pharmacology – the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 5- to 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors. Several orexin receptor antagonists are in development for potential use in sleep disorders. The first of these, suvorexant, has been on the market in the United States since 2015. There were two orexin agonists under development . Ligands Several drugs acting on the orexin system are under development, either orexin agonists for the treatment of conditions such as narcolepsy, or orexin antagonists for insomnia. In Augus ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Danavorexton
Danavorexton (developmental code name TAK-925) is a selective orexin 2 receptor agonist. It is a small-molecule compound and is administered intravenously. The compound was found to dose-dependently produce wakefulness to a similar degree as modafinil in a phase 1 clinical trial.Evans, R., Hazel, J., Faessel, H., Wu, J., Hang, Y., Alexander, R., ... & Hartman, D. (2019). Results of a phase 1, 4-period crossover, placebo-controlled, randomized, single dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925, a novel orexin 2 receptor agonist, in sleep-deprived healthy adults, utilizing modafinil as an active comparator. Sleep Medicine, 64, S106. https://scholar.google.com/scholar?cluster=10933819770107034612 As of March 2021, danavorexton is under development for the treatment of narcolepsy, idiopathic hypersomnia, and sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemical Structure
A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together, and can be represented using structural formulae and by molecular models; complete electronic structure descriptions include specifying the occupation of a molecule's molecular orbitals. Structure determination can be applied to a range of targets from very simple molecules (e.g., diatomic oxygen or nitrogen), to very complex ones (e.g., such as protein or DNA). Background Theories of chemical structure were first developed by August Kekulé, Archibald Scott Couper, and Aleksandr Butlerov, among others, from about 1858. These theories were first to state that chemical compounds are not a random cluster of atoms and functional groups, but rather had a definite o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drug Safety
Term Given By Tushar Sharma (UPES Batch 2025) Pharmacovigilance (PV, or PhV), also known as drug safety, is the pharmaceutical science relating to the "collection, detection, assessment, monitoring, and prevention" of adverse effects with pharmaceutical products. The etymological roots for the word "pharmacovigilance" are: (Greek for drug) and (Latin for to keep watch). As such, pharmacovigilance heavily focuses on adverse drug reactions (ADR), which are defined as any response to a drug which is noxious and unintended, including lack of efficacy (the condition that this definition only applies with the doses normally used for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological disorder function was excluded with the latest amendment of the applicable legislation). Medication errors such as overdose, and misuse and abuse of a drug as well as drug exposure during pregnancy and breastfeeding, are also of interest, even without an adve ... [...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] |
Phases Of Clinical Research
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ... [...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 mouth ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Orexin Receptor 1
Orexin receptor type 1 (Ox1R or OX1), also known as hypocretin receptor type 1 (HcrtR1), is a protein that in humans is encoded by the HCRTR1 gene. Function The orexin 1 receptor (OX1), is a G-protein coupled receptor that is heavily expressed in projections from the lateral hypothalamus and is involved in the regulation of feeding behaviour. OX1 selectively binds the orexin-A neuropeptide. It shares 64% identity with OX2. Ligands Agonists * Orexin-A Antagonists * RTIOX-276 - Selective OX1 antagonist * ACT-335827 - Selective OX1 antagonist * Almorexant - Dual OX1 and OX2 antagonist * Lemborexant - Dual OX1 and OX2 antagonist * Nemorexant - Dual OX1 and OX2 antagonist * SB-334,867 - Selective OX1 antagonist * SB-408,124 - Selective OX1 antagonist * SB-649,868 - Dual OX1 and OX2 antagonist * Suvorexant - Dual OX1 and OX2 antagonist See also * Orexin receptor The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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