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| CAS Number | |
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| Chemical and physical data | |
| Formula | C25H28N4OS |
| Molar mass | 432.59 g·mol−1 |
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GAT100 is a negative allosteric modulator of the cannabinoid CB1 receptor. [1] [2]
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| Identifiers | |
|---|---|
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| CAS Number | |
| ChemSpider | |
| Chemical and physical data | |
| Formula | C25H28N4OS |
| Molar mass | 432.59 g·mol−1 |
| 3D model (JSmol) | |
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GAT100 is a negative allosteric modulator of the cannabinoid CB1 receptor. [1] [2]
In biochemistry, allosteric regulation is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates– a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains. Cannabinoid receptors are activated by three major groups of ligands: endocannabinoids; phytocannabinoids ; and synthetic cannabinoids. All endocannabinoids and phytocannabinoids are lipophilic.
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 Latin 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.
Desformylflustrabromine (dFBr) is a monomethyltryptamine derivative which was first isolated as a secondary metabolite of the marine bryozoan Flustra foliacea.
The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in humans, is encoded by the CHRM4 gene.
Cannabinoid receptor 1 (CB1), is a G protein-coupled cannabinoid receptor that in humans is encoded by the CNR1 gene. The human CB1 receptor is expressed in the peripheral nervous system and central nervous system. It is activated by endocannabinoids, a group of retrograde neurotransmitters that include anandamide and 2-arachidonoylglycerol (2-AG); plant phytocannabinoids, such as docosatetraenoylethanolamide found in wild daga, the compound THC which is an active constituent of the psychoactive drug cannabis; and synthetic analogs of THC. CB1 is antagonized by the phytocannabinoid tetrahydrocannabivarin (THCV).
Metabotropic receptor 4 is a protein that in humans is encoded by the GRM4 gene.
The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcoholic beverages, function as psychoactive drugs. The site that an allosteric modulator binds to is not the same one to which an endogenous agonist of the receptor would bind. Modulators and agonists can both be called receptor ligands.
SKF-83,959 is a synthetic benzazepine derivative used in scientific research which acts as an agonist at the D1–D2 dopamine receptor heteromer. It behaves as a full agonist at the D1 protomer and a high-affinity partial agonist at the D2 protomer. It was further shown to act as an allosteric modulator of the sigma-1 receptor. SKF-83,959 additionally inhibits sodium channels as well as delayed rectifier potassium channels. SKF-83,959 is a racemate that consists of the R-(+)- and S-(−)-enantiomers MCL-202 and MCL-201, respectively.
An opioidergic agent is a chemical which functions to directly modulate the opioid neuropeptide systems in the body or brain. Examples include opioid analgesics such as morphine and opioid antagonists such as naloxone. Opioidergics also comprise allosteric modulators and enzyme affecting agents like enkephalinase inhibitors.
Hemopressin (Hp) is an alpha hemoglobin fragment with the sequence PVNFKFLSH, originally identified in extracts of rat brain using an enzyme capture technique. It binds cannabinoid receptors, acting as an inverse agonist at CB1 receptors. Longer forms of hemopressin containing 2-3 additional amino acids on the N-terminus have been identified in extracts of mouse brain. These longer hemopressin peptides, named RVD-Hpα and VD-Hpα, bind to CB1 receptors and were originally reported to be agonists. In addition to the Hp peptides from alpha hemoglobin, a related peptide from beta hemoglobin has been found in mouse brain extracts; this peptide, named VD-Hpβ, is also an agonist at CB1 cannabinoid receptors. Hemopressin is not an endogenous peptide but rather an extraction artefact. The only endogenous peptide found endogenously at physiological conditions is RVD-hemopressin (pepcan-12), which has more recently been shown to be a negative allosteric modulator of CB1 receptors and positive allosteric modulator of CB2 receptors. RVD-hemopressin (pepcan-12) is generated from a pro-peptide called pepcan-23 and these peptides are exclusively found in noradrenergic neurons in the brain and in the adrenal medulla.
SR144528 is a drug that acts as a potent and highly selective CB2 receptor inverse agonist, with a Ki of 0.6 nM at CB2 and 400 nM at the related CB1 receptor. It is used in scientific research for investigating the function of the CB2 receptor, as well as for studying the effects of CB1 receptors in isolation, as few CB1 agonists that do not also show significant activity as CB2 agonists are available. It has also been found to be an inhibitor of sterol O-acyltransferase, an effect that appears to be independent from its action on CB2 receptors.
SDB-006 is a drug that acts as a potent agonist for the cannabinoid receptors, with an EC50 of 19 nM for human CB2 receptors, and 134 nM for human CB1 receptors. It was discovered during research into the related compound SDB-001 which had been sold illicitly as "2NE1". SDB-006 metabolism has been described in literature.
Mitragynine pseudoindoxyl is a rearrangement product of 7-hydroxymitragynine and active metabolite of mitragynine. It is an analgesic being more potent than morphine.
ZCZ-011 is a positive allosteric modulator of the cannabinoid CB1 receptor.
PSNCBAM-1 is a negative allosteric modulator of the cannabinoid CB1 receptor.
AM-11245 is a drug which is a cannabinoid agonist from the classical cannabinoid family. It has high affinity and efficacy at both the CB1 and CB2 cannabinoid receptors, with a Ki of 0.4nM at both CB1 and CB2, and an EC50 of ~0.06nM at CB1 and 0.2nM at CB2, making it one of the most potent cannabinoid agonists identified to date.
AEF0117 (3β-(4-methoxybenzyloxy)pregn-5-en-20-one) is a compound derived from pregnenolone by Aelis Farma, which acts as a biased allosteric modulator of the cannabinoid CB1 receptor, representing a new class of compounds referred to as CB1-selective signalling-specific inhibitors (CB1-SSi). It binds to an allosteric site on the CB1 receptor and modifies the downstream signalling produced as a result of CB1 activation, preventing CB1 mediated changes to mitogen-activated protein kinase (MAPK) phosphorylation but without affecting the signalling mediated by cyclic AMP. Unlike pregnenolone, AEF0117 is specific for the CB1-SSi activity and lacks the neurosteroid action typical of many structurally related compounds.
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