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E-52862
E-52862, also known as sigma-1 receptor antagonist (S1A, S1RA), as well as MR-309, is a selective sigma-1 receptor antagonist, with a reported binding affinity of ''K''i = 17.0 ± 7.0 nM, selective over the sigma-2 receptor and against a panel of other 170 receptors, enzymes, transporters and ion channels. In preclinical studies, S1RA has demonstrated efficacy in relieving neuropathic pain and pain in other sensitizing conditions, associated with an improvement of the emotional negative state. S1RA is being developed by Esteve for the treatment of neuropathic pain and the potentiation of opioid analgesia and has successfully completed Phase I clinical trials showing good safety and tolerability, and a pharmacokinetic profile compatible with once a day oral administration. Phase II clinical trials are currently underway, making S1RA the first selective sigma-1 receptor antagonist evaluated in humans for these conditions. See also * List of investigational analgesics Reference ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
List Of Investigational Analgesics
This is a list of investigational analgesics, or analgesics 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.'' Opioid receptor modulators * Axelopran/oxycodone – combination of a centrally active μ-opioid receptor agonist and a peripherally selective μ-, κ-opioid receptor, κ-, and δ-opioid receptor receptor antagonist, antagonist. * Cebranopadol (GRT-6005) – non-selective μ-opioid receptor, nociceptin receptor, and δ-opioid receptor full agonist and κ-opioid receptor partial agonist * Desmetramadol (''O''-desmethyltramadol; Omnitram) – μ-opioid receptor agonist, norepinephrine reuptake inhibitor (NRI), and 5-HT2C receptor, 5-HT2C receptor antagonist. * Lexanopadol (GRT-6006, GRT13106G) – non-selective opioid receptor agonist * Oxycodone/naltrexone – combination of a μ-opioid receptor agonist and a μ- and κ-opioid ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Binding Selectivity
Binding selectivity is defined with respect to the binding of ligands to a substrate forming a complex. Binding selectivity describes how a ligand may bind more preferentially to one receptor than another. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate. Binding selectivity is of major importance in biochemistry and in chemical separation processes. Selectivity coefficient The concept of selectivity is used to quantify the extent to which one chemical substance, A, binds each of two other chemical substances, B and C. The simplest case is where the complexes formed have 1:1 stoichiometry. Then, the two interactions may be characterized by equilibrium constants ''K''AB and ''K''AC.The constant used here are ''association'' constants. ''Dissociation'' constants are used in some contexts. A dissociation constant is the reciprocal of an association constant. : + B AB; \mathit K_ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sigma-1 Receptor
The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gene. The σ1 receptor is a transmembrane protein expressed in many different tissue types. It is particularly concentrated in certain regions of the central nervous system. It has been implicated in several phenomena, including cardiovascular function, schizophrenia, clinical depression, the effects of cocaine abuse, and cancer. Much is known about the binding affinity of hundreds of synthetic compounds to the σ1 receptor. An endogenous ligand for the σ1 receptor has yet to be conclusively identified, but tryptaminergic trace amines and neuroactive steroids have been found to activate the receptor. Especially progesterone, but also testosterone, pregnenolone sulfate, and dehydroepiandrosterone sulfate (DHEA-S) bind to the σ1 receptor. C ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Receptor Antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of receptor proteins.Pharmacology Guide: In vitro pharmacology: concentration-response curves " '' GlaxoWellcome.'' Retrieved on December 6, 2007. They are sometimes called blockers; examples include alpha blockers, |
Binding Affinity
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure. Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association or docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of ligan ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sigma-2 Receptor
The sigma-2 receptor (σ2R) is a sigma receptor subtype that has attracted attention due to its involvement in diseases such as cancer and neurological diseases. It is currently under investigation for its potential diagnostic and therapeutic uses. Although the sigma-2 receptor was identified as a separate pharmacological entity from the sigma-1 receptor in 1990, the gene that codes for the receptor was identified as TMEM97 only in 2017. TMEM97 was shown to regulate the cholesterol transporter NPC1 and to be involved in cholesterol homeostasis. The sigma-2 receptor is a four-pass transmembrane protein located in the endoplasmic reticulum. It has been found to play a role in both hormone signaling and calcium signaling, in neuronal signaling, in cell proliferation and death, and in binding of antipsychotics. Classification The sigma-2 receptor is located in the lipid raft. The sigma-2 receptor is found in several areas of the brain, including high densities in the cerebellum, m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neuropathic Pain
Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous and/or episodic (paroxysmal) components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, "pins and needles" sensations, numbness and itching. Up to 7%-8% of the European population is affected, and in 5% of persons it may be severe. Neuropathic pain may result from disorders of the peripheral nervous system or the central nervous system (brain and spinal cord). Thus, neuropathic pain may be divided into peripheral neuropathic pain, central neuropathic pain, or mixed (peripheral and central) neuropathic pain. Neuropathic pain may occur in isolation or in combination with other forms of pain. Medical treatments focus on identifying the underlying cause and relieving pain. In cases of neuropathy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage." In medical diagnosis, pain is regarded as a symptom of an underlying condition. Pain motivates the individual to withdraw from damaging situations, to protect a damaged body part while it heals, and to avoid similar experiences in the future. Most pain resolves once the noxious stimulus is removed and the body has healed, but it may persist despite removal of the stimulus and apparent healing of the body. Sometimes pain arises in the absence of any detectable stimulus, damage or disease. Pain is the most common reason for physician consultation in most developed countries. It is a major symptom in many medical conditions, and can interfere with a person's quality of life and general functioning. Simple ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Esteve
Esteve is a Spanish international pharmaceutical company headquartered in Barcelona Barcelona ( , , ) is a city on the coast of northeastern Spain. It is the capital and largest city of the autonomous community of Catalonia, as well as the second most populous municipality of Spain. With a population of 1.6 million within ci .... Since its founding in 1929, Esteve has extended its commercial activity to more than 100 countries around the world. History The company's origins date back to 1929, when Dr. Antoni Esteve i Subirana, researcher and entrepreneur, founded the firm. Now the family-owned company has around 2,900 employees and operates in different countries and continents, through subsidiary companies in Europe and the US and through production centers in Mexico and China, with products directly present in 40 countries and indirectly present, through licensing and distribution agreements, in over 60 countries around the world. Company focus Esteve focuses mainly on ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyrazoles
Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazole is a weak base, with p''K''b 11.5 (p''K''a of the conjugate acid 2.49 at 25 °C). Pyrazoles are also a class of compounds that have the ring C3N2 with adjacent nitrogen atoms. Notable drugs containing a pyrazole ring are celecoxib (celebrex) and the anabolic steroid stanozolol. Preparation and reactions Pyrazoles are synthesized by the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation: : Substituted pyrazoles are prepared by condensation of 1,3-diketones with hydrazine ( Knorr-type reactions). For example, acetylacetone and hydrazine gives 3,5-dimethylpyrazole: :CH3C(O)CH2C(O)CH3 + N2H4 → (CH3)2C3HN2H + 2 H2O History The term pyrazole was given to this class of compounds by German ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
