AM-1235
Encyclopedia
AM-1235 is a drug which acts as a potent and reasonably selective agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

 for the cannabinoid receptor
Cannabinoid receptor
The cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains...

 CB1, with a Ki
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...

 of 1.5nM at CB1 compared to 20.4nM at CB2
Cannabinoid receptor 2 (macrophage)
Cannabinoid receptor 2 , also known as CB2 or CNR2, is a G protein-coupled receptor from the cannabinoid receptor family, which in humans is encoded by the CNR2 gene...

. While the 6-nitro substitution on the indole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...

 ring reduces affinity for both CB1 and CB2 relative to the unsubstituted parent compound AM-2201
AM-2201
AM-2201 discovered by Chemist Tyler Merrill, is a drug which acts as a potent but unselective agonist for the cannabinoid receptor CB1, with a Ki of 1.0nM at CB1 and 2.6nM at CB2...

, CB2 affinity is reduced much more, resulting in a CB1 selectivity of around 13x. This is in contrast to other related compounds such as AM-1221
AM-1221
AM-1221 is a drug which acts as a potent and selective agonist for the cannabinoid receptor CB2, with a Ki of 0.28nM at CB2 and 52.3nM at the CB1 receptor, giving it around 180x selectivity for CB2. The 2-methyl and 6-nitro groups on the indole ring both tend to increase CB2 affinity while...

where a 6-nitro substitution instead confers significant selectivity for CB2.
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