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| ECHA InfoCard | 100.209.196 |
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| Formula | C24H26N2O6 |
| Molar mass | 438.480 g·mol−1 |
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JTE-907 is a drug used in scientific research that acts as a selective CB2 inverse agonist. [1] [2] It has antiinflammatory effects in animal studies, [3] thought to be mediated by an interaction between the CB2 receptor and IgE. [4]
WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure.
Cannabinoid receptor 1 (CB1), is a G protein-coupled cannabinoid receptor that in humans is encoded by the CNR1 gene. And discovered, by determination and characterization in 1988, and cloned in 1990 for the first time. The human CB1 receptor is expressed in the peripheral nervous system and central nervous system. It is activated by endogenous cannabinoids called endocannabinoids, a group of retrograde neurotransmitters that include lipids, such as anandamide and 2-arachidonoylglycerol; plant phytocannabinoids, such as docosatetraenoylethanolamide found in wild daga, the compound tetrahydrocannabinol which is an active constituent of the psychoactive drug cannabis; and synthetic analogs of tetrahydrocannabinol. CB1 is antagonized by the phytocannabinoid tetrahydrocannabivarin at low doses and at higher doses, it activate the CB1 receptor as an agonist, but with less potency than tetrahydrocannabinol.
The cannabinoid receptor 2(CB2), is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. It is closely related to the cannabinoid receptor 1 (CB1), which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of tetrahydrocannabinol (THC), the active agent in cannabis, and other phytocannabinoids. The principal endogenous ligand for the CB2 receptor is 2-Arachidonoylglycerol (2-AG).
NESS-0327 is a drug used in scientific research which acts as an extremely potent and selective antagonist of the cannabinoid receptor CB1. It is much more potent an antagonist, and more selective for the CB1 receptor over CB2, than the more commonly used ligand rimonabant, with a Ki at CB1 of 350fM (i.e. 0.00035nM) and a selectivity of over 60,000x for CB1 over CB2. Independently, two other groups have described only modest nanomolar CB1 affinity for this compound (125nM and 18.4nM). Also unlike rimonabant, NESS-0327 does not appear to act as an inverse agonist at higher doses, instead being a purely neutral antagonist which blocks the CB1 receptor but does not produce any physiological effect of its own.
A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest in research and development of CBR antagonists. Cannabidiol (CBD), a naturally occurring cannabinoid and a non-competitive CB1/CB2 receptor antagonist, as well as Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.
GW-405,833 (L-768,242) is a drug that acts as a potent and selective partial agonist for the cannabinoid receptor subtype CB2, with an EC50 of 0.65 nM and selectivity of around 1200x for CB2 over CB1 receptors. Animal studies have shown it to possess antiinflammatory and anti-hyperalgesic effects at low doses, followed by ataxia and analgesic effects when the dose is increased. Selective CB2 agonist drugs such as GW-405,833 are hoped to be particularly useful in the treatment of allodynia and neuropathic pain for which current treatment options are often inadequate.
AM-1241 (1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole) is a chemical from the aminoalkylindole family that acts as a potent and selective agonist for the cannabinoid receptor CB2, with a Ki of 3.4 nM at CB2 and 80 times selectivity over the related CB1 receptor. It has analgesic effects in animal studies, particularly against "atypical" pain such as hyperalgesia and allodynia. This is thought to be mediated through CB2-mediated peripheral release of endogenous opioid peptides, as well as direct activation of the TRPA1 channel. It has also shown efficacy in the treatment of amyotrophic lateral sclerosis in animal models.
A-836,339 is a drug developed by Abbott Laboratories that acts as a potent cannabinoid receptor full agonist. It is selective for CB2, with Ki values of 0.64 nM at CB2 vs 270 nM at the psychoactive CB1 receptor, but while it exhibits selective analgesic, anti-inflammatory and anti-hyperalgesic effects at low doses, its high efficacy at both targets results in typical cannabis-like effects appearing at higher doses, despite its low binding affinity for CB1. In 2012 A-836,339 was detected via X-ray crystallography in a "dubious product" sold in Japan, though the product was described as a white powder, not herbal incense, it was suggested to be for human consumption.
A-834,735 is a drug developed by Abbott Laboratories that acts as a potent cannabinoid receptor full agonist at both the CB1 and CB2 receptors, with a Ki of 12 nM at CB1 and 0.21 nM at CB2. Replacing the aromatic 3-benzoyl or 3-naphthoyl group found in most indole derived cannabinoids with the 3-tetramethylcyclopropylmethanone group of A-834,735 and related compounds imparts significant selectivity for CB2, with most compounds from this group found to be highly selective CB2 agonists with little affinity for CB1. However, low nanomolar CB1 binding affinity is retained with certain heterocyclic 1-position substituents such as (N-methylpiperidin-2-yl)methyl (cf. AM-1220, AM-1248), or the (tetrahydropyran-4-yl)methyl substituent of A-834,735, resulting in compounds that still show significant affinity and efficacy at both receptors despite being CB2 selective overall.
AM-630 (6-Iodopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB2, with a Ki of 32.1 nM at CB2 and 165x selectivity over CB1, at which it acted as a weak partial agonist. It is used in the study of CB2 mediated responses and has been used to investigate the possible role of CB2 receptors in the brain. AM-630 is significant as one of the first indole derived cannabinoid ligands substituted on the 6-position of the indole ring, a position that has subsequently been found to be important in determining affinity and efficacy at both the CB1 and CB2 receptors, and has led to the development of many related derivatives.
AM-2233 is a drug that acts as a highly potent full agonist for the cannabinoid receptors, with a Ki of 1.8 nM at CB1 and 2.2 nM at CB2 as the active (R) enantiomer. It was developed as a selective radioligand for the cannabinoid receptors and has been used as its 131I derivative for mapping the distribution of the CB1 receptor in the brain. AM-2233 was found to fully substitute for THC in rats, with a potency lower than that of JWH-018 but higher than WIN 55,212-2.
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.
JTE 7-31 is a selective cannabinoid receptor agonist invented by Japan Tobacco. It is a reasonably highly selective CB2 agonist, but still retains appreciable affinity at CB1, with a Ki of 0.088nM at CB2 vs 11nM at CB1.
MN-25 (UR-12) is a drug invented by Bristol-Myers Squibb, that acts as a reasonably selective agonist of peripheral cannabinoid receptors. It has moderate affinity for CB2 receptors with a Ki of 11 nM, but 22x lower affinity for the psychoactive CB1 receptors with a Ki of 245 nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a Ki of 8 nM at CB1 and 29 nM at CB2, which contrasts with the usual trend of 2-methyl derivatives having increased selectivity for CB2 (cf. JWH-018 vs JWH-007, JWH-081 vs JWH-098).
S-444,823 is a drug developed by Shionogi which is a cannabinoid agonist. It was developed as an antipruritic, and has moderate selectivity for the CB2 subtype, having a CB2 affinity of 18nM, and 32x selectivity over the CB1 receptor. In animal studies it showed analgesic effects and strongly reduced itching responses, but without producing side effects such as sedation and catalepsy that are seen with centrally acting CB1 agonists.
4-O-Methylhonokiol is a neolignan, a type of phenolic compound. It is found in the bark of Magnolia grandiflora and in M. virginiana flowers.
CID16020046 is a compound which acts as an inverse agonist at the former orphan receptor GPR55, and may be the first selective inverse agonist characterised for this receptor. It was found to block a number of GPR55 mediated responses such as wound healing and activation of immune system T-cells and B-cells, as well as showing inverse agonist activity in the absence of GPR55 agonist stimulation. However while it was found to have good selectivity over the related CB1 and CB2 cannabinoid receptors as well as a number of other targets, CID16020046 has not yet been tested against another related receptor GPR18, so its selectivity for GPR55 over this target has not been established. It has antiinflammatory actions, has been used to study the interaction between GPR55 mediated and CB1 mediated activity, and research using this compound has revealed a role for GPR55 in learning and memory.
S-777,469 is a drug developed by Shionogi which is a cannabinoid receptor agonist, with 128x selectivity for the CB2 subtype, having a CB2 affinity of 36nM, and a CB1 affinity over 4600nM.
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