AM6538 is a long-acting, high-affinity, pseudo-irreversible cannabinoid (CB) antagonist. AM6538 is a structural analog of rimonabant. AM6538 effectively evaluates the apparent efficacy of cannabinoid complete and partial agonists. AM6538 may be useful in future studies requiring a temporary reduction in cannabinoid receptor availability. AM-6538 is a reagent for click chemistry. It has Alkyne groups and could undergo CuAAc (copper-catalyzed azide-alkyne cycloaddition reaction) with compounds bearing Azide groups.

Physicochemical Properties

Molecular Formula	C26H25CL2N5O4
Molecular Weight	542.413803815842
Exact Mass	541.128
CAS #	1245626-00-9
PubChem CID	46912833
Appearance	White to off-white solid powder
LogP	6.8
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	37
Complexity	847
Defined Atom Stereocenter Count	0
InChi Key	KXXKUWQMQUYUSE-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H25Cl2N5O4/c1-18-24(26(34)30-31-14-4-2-5-15-31)29-32(23-13-12-21(27)17-22(23)28)25(18)20-10-8-19(9-11-20)7-3-6-16-37-33(35)36/h8-13,17H,2,4-6,14-16H2,1H3,(H,30,34)
Chemical Name	4-[4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl]but-3-ynyl nitrate
Synonyms	AM6538 AM 6538 AM-6538
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	AM6538 is a cannabinoid antagonist that binds to the CB1 receptor expressed in HEK-293 cells in a wash-stable manner [1].
ln Vivo	Mice treated with AM6538 (1~10 mg/kg) do not experience the analgesic effects of cannabinoid agonists [1]. There was a partial restoration of AM4054's impact with AM6538 (10 mg/kg). All cannabis agonists' tau is dose-dependently reduced by AM6538, indicating a decrease in the number of accessible receptors. Up to seven days following therapy, AM6538 causes strong, long-lasting antagonistic effects on THC's dose-response function [1].
References	[1]. Long-Lasting In Vivo Effects of the Cannabinoid CB1 Antagonist AM6538. J Pharmacol Exp Ther. 2018;364(3):485-493.

Solubility Data

Solubility (In Vitro)

DMSO : ~180 mg/mL (~331.85 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 4.5 mg/mL (8.30 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 45.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8436 mL	9.2181 mL	18.4362 mL
	5 mM	0.3687 mL	1.8436 mL	3.6872 mL
	10 mM	0.1844 mL	0.9218 mL	1.8436 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.