Cat. No.: HY-15443

AM251

26 Cited Publications

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Based on 26 publication(s) in Google Scholar

AM251 is a selective cannabinoid 1 (CB1) receptor antagonist with an IC₅₀ of 8 nM. AM251 also acts as a potent GPR55 agonist with an EC₅₀ of 39 nM.

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Pureté: 99.09%
CAS No.: 183232-66-8
Formule: C₂₂H₂₁Cl₂IN₄O
Masse moléculaire:555.24

Stockage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

AM251 Chemical Structure

CAS No.: 183232-66-8

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Activité biologique
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (26)
Solvant et solubilité
- In Vitro
- In Vivo
Protocole
Pureté et documentation
Références
Help & FAQs
Classifications
Bioz

Activité biologique

Description

AM251 is a selective cannabinoid 1 (CB1) receptor antagonist with an IC₅₀ of 8 nM. AM251 also acts as a potent GPR55 agonist with an EC₅₀ of 39 nM^[1]^[2]^[3].

IC₅₀ & Target

IC50: 8 nM (CB1 receptor)^[1]

Voir tous les produits spécifiques à Isoform Cannabinoid Receptor :

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	IC₅₀	0.32 nM Compound: AM-251	Displacement of [3H]SR-141716 from human wild type CB1R expressed in CHO cells Displacement of [3H]SR-141716 from human wild type CB1R expressed in CHO cells	[PMID: 18333607]
CHO	IC₅₀	0.59 nM Compound: AM-251	Displacement of [3H]SR-141716 from human CBR1 S383A mutant expressed in CHO cells Displacement of [3H]SR-141716 from human CBR1 S383A mutant expressed in CHO cells	[PMID: 18333607]
CHO	IC₅₀	190 nM Compound: AM-251	Displacement of [3H]CP-55940 from human CB1R W279A mutant expressed in CHO cells Displacement of [3H]CP-55940 from human CB1R W279A mutant expressed in CHO cells	[PMID: 18333607]
CHO	IC₅₀	3.5 nM Compound: AM-251	Displacement of [3H]CP-55940 from human wild type CB1R expressed in CHO cells Displacement of [3H]CP-55940 from human wild type CB1R expressed in CHO cells	[PMID: 18333607]
CHO	IC₅₀	30 nM Compound: AM-251	Displacement of [3H]CP-55940 from human CB1R F200L mutant expressed in CHO cells Displacement of [3H]CP-55940 from human CB1R F200L mutant expressed in CHO cells	[PMID: 18333607]
CHO	IC₅₀	340 nM Compound: AM-251	Displacement of [3H]CP-55940 from human CB1R F170L mutant expressed in CHO cells Displacement of [3H]CP-55940 from human CB1R F170L mutant expressed in CHO cells	[PMID: 18333607]
CHO	IC₅₀	60 nM Compound: AM-251	Displacement of [3H]CP-55940 from human CB1R K192L mutant expressed in CHO cells Displacement of [3H]CP-55940 from human CB1R K192L mutant expressed in CHO cells	[PMID: 18333607]
HEK293	EC₅₀	0.63 μM Compound: AM251	Agonist activity at human GPR55 expressed in HEK293 cells assessed as increase in oscillation Ca2+ transients by fura-2 dye based fluorescence analysis Agonist activity at human GPR55 expressed in HEK293 cells assessed as increase in oscillation Ca2+ transients by fura-2 dye based fluorescence analysis	10.1039/C3MD00394A
Sf9	EC₅₀	0.07 μM Compound: AM251	Inverse agonist activity at human CB1 receptor expressed in Sf9 cells coexpressing Gbeta1gamma2 and RSG4 assessed as degradation of [gamma-33P]GTP after 20 mins by steady-state GTPase assay Inverse agonist activity at human CB1 receptor expressed in Sf9 cells coexpressing Gbeta1gamma2 and RSG4 assessed as degradation of [gamma-33P]GTP after 20 mins by steady-state GTPase assay	[PMID: 25096297]

In Vitro

AM251 is a CB1 receptor antagonist/inverse agonist. AM251 produces an agonist response in HEK293 cells, similar to that found in the yeast expression system^[2].
AM-251 reduces cholesteryl ester synthesis in unstimulated and acetylated LDL-stimulated Raw 264.7 macrophages, CB2^+/+ and CB2^-/- peritoneal macrophages^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

The CB1 antagonist AM251 (3 mg/kg, i.p.) decreases capsaicin-evoked nocifensive behavior. This suppressive effect is genotype dependent, and the interaction between the effects of genotype and AM251 approached significance. Planned comparisons reveal that AM251 reduces nocifensive behaviors in fatty-acid amide hydrolase (FAAH) KO mice (p<0.01) but fails to alter nocifensive behavior in WT mice (p>0.2) relative to their respective vehicle controls. AM251 (3 mg/kg, i.p.) reduces the duration of heat hypersensitivity in FAAH KO (F_1,9=21.43, p<0.01) but not WT mice (p>0.3). AM251 suppresses capsaicin-evoked heat hypersensitivity in a time-dependent manner in FAAH KO (F_5,9=4.349, p<0.01) but not in WT mice (p>0.3). Post-hoc analysis reveals that FAAH KO mice receiving vehicle (i.p.) display heightened thermal hypersensitivity at 30 (p<0.05), 60 (p<0.05), and 90 (p<0.001) minutes post-capsaicin in comparison to FAAH KO animals receiving AM251)^[4].
One-way ANOVA shows that AM251 (AM-251) injected into the rats significantly decreases both of the percentage of entries in the open arms and time spent in the open arms, compare to controls. The Tukey-Kramer test analysis reveals a significant reduction for the doses of 1 mg/kg (P<0.05) and 5 mg/kg (P<0.01) compare to control rats in the time spent in the open arms. Also, AM251 significantly decreases percentage of entries in the open arms for the doses of 1 and 5 mg/kg (P<0.05)^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Chemical Information

CAS No. 183232-66-8
Appearance Solid
Masse moléculaire 555.24
Formule C₂₂H₂₁Cl₂IN₄O
Color White to off-white
SMILES

O=C(C1=NN(C2=CC=C(Cl)C=C2Cl)C(C3=CC=C(I)C=C3)=C1C)NN4CCCCC4
Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (26)

All Cell Migration/Invasion AssayIn Vivo Efficacy StudyWB

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Journal Impact Factor

Signal Transduct Target Ther

CB1R-stabilized NLRP3 inflammasome drives antipsychotics cardiotoxicity. [Abstract]

2022 Jun 24;7(1):190. PMID: 35739093
Cell Host Microbe

Microbiota-driven gut-brain signaling underlies antidepressant effects of a GLP-1 analog. [Abstract]

2026 Jun 10;34(6):1000-1017.e5. PMID: 42269582
EBioMedicine

Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis. [Abstract]

2020 Mar;53:102696. PMID: 32143183

AM251 purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2020 Mar;53:102696. [Abstract]

Invasion of shControl/shABHD6 SPC-A-1 and A549 cells with or without 50 nM AM251 (8 h) treatment.

AM251 purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2020 Mar;53:102696. [Abstract]

Migration of shControl/shABHD6 SPC-A-1 and A549 cells with or without 50 nM AM251 (8 h) treatment.
Acta Pharmacol Sin

Differential regulation of pruritic sensation and emotion by cannabinoid type 1 receptors on mPFC glutamatergic and GABAergic neurons. [Abstract]

2025 Apr;46(4):904-921. PMID: 39663420

AM251 purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2025 Apr;46(4):904-921. [Abstract]

AM251 (2.5 mg/mL; 200 nL was microinjected into the mPFC at 30 nL/min via a cannula-connected pump) administration resulted in a significant reduction in chronic itch-induced scratching.

AM251 purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2025 Apr;46(4):904-921. [Abstract]

Representative image showing the spatial location of CQ:AM251 (2.5 mg/mL; 200 nL was microinjected into the mPFC at 30 nL/min via a cannula-connected pump) mice before and after CQ conditioning.
Sci China Life Sci

NPC1-regulated dynamic of clathrin-coated pits is essential for viral entry. [Abstract]

2022 Feb;65(2):341-361. PMID: 34047913
J Headache Pain

Activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in a chronic migraine rat model. [Abstract]

2023 Apr 21;24(1):44. PMID: 37085778
Cell Rep

Cannabinoids Rescue Cocaine-Induced Seizures by Restoring Brain Glycine Receptor Dysfunction. [Abstract]

2020 Mar 24;30(12):4209-4219.e7. PMID: 32209479
Food Biosci

2026 Apr 2;79:108812.
Eur J Pharmacol

Cannabidiol represses miR-143 to promote cardiomyocyte proliferation and heart regeneration after myocardial infarction. [Abstract]

2024 Jan 15:963:176245. PMID: 38052413
Int J Mol Sci

Intraplantar β-Caryophyllene Alleviates Pain and Inflammation in STZ-Induced Diabetic Peripheral Neuropathy via CB2 Receptor Activation. [Abstract]

2025 May 7;26(9):4430. PMID: 40362667
Int J Mol Sci

Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats. [Abstract]

2022 Dec 23;24(1):240. PMID: 36613692
Mol Neurobiol

Electroacupuncture Exerts Analgesic Effects by Restoring Hyperactivity via Cannabinoid Type 1 Receptors in the Anterior Cingulate Cortex in Chronic Inflammatory Pain. [Abstract]

2024 May;61(5):2949-2963. PMID: 37957422
Mol Neurobiol

mGluR5-Mediated eCB Signaling in the Nucleus Accumbens Controls Vulnerability to Depressive-Like Behaviors and Pain After Chronic Social Defeat Stress. [Abstract]

2021 Oct;58(10):4944-4958. PMID: 34227060
Psychiatry Res

Inhibition of CB1 receptor alleviates electroconvulsive shock-induced memory impairment by regulating hippocampal synaptic plasticity in depressive rats. [Abstract]

2021 Jun:300:113917. PMID: 33848965
Sci Rep

Targeting CB1 and TRPM8 receptors to counteract CD8+ T cell exhaustion. [Abstract]

2026 Apr 10;16(1):16876. PMID: 41963448
Neurochem Res

Gut Microbiota-Mediated Alterations of Hippocampal CB1R Regulating the Diurnal Variation of Cognitive Impairment Induced by Hepatic Ischemia-Reperfusion Injury in Mice. [Abstract]

2024 Aug;49(8):2165-2178. PMID: 38824460
Front Mol Neurosci

MPTP-Induced Dopamine Depletion in Basolateral Amygdala via Decrease of D2R Activation Suppresses GABAA Receptors Expression and LTD Induction Leading to Anxiety-Like Behaviors. [Abstract]

2017 Aug 7;10:247. PMID: 28824377
Eur J Pain

Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation. [Abstract]

2017 May;21(5):804-814. PMID: 28107590
Am J Physiol Renal Physiol

Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats. [Abstract]

2017 Mar 1;312(3):F482-F488. PMID: 27927655
Neuroscience

Cannabinoid Receptor Type 2 Agonist Reduces Morphine Tolerance via Mitogen Activated Protein Kinase Phosphatase Induction and Mitogen Activated Protein Kinase Dephosphorylation. [Abstract]

2022 Jan 1:480:56-64. PMID: 34774714
Clin Exp Pharmacol Physiol

Spermidine prevents high glucose-induced senescence in HT-22 cells by upregulation of CB1 receptor. [Abstract]

2018 Aug;45(8):832-840. PMID: 29699000

AM251 purchased from MedChemExpress. Usage Cited in: Clin Exp Pharmacol Physiol. 2018 Aug;45(8):832-840. [Abstract]

Pretreatment of AM251 (10 nM, for 30 minutes) reverses the Spermidine (Spd)-provided suppression on the high glucose (HG)-induced upregulations of p16^INK4a in HT-22 cells.
The George Washington University

2026.
bioRxiv

2025 Nov 28.
SSRN

2025 Mar 24.
Patent

US20230192657A1.
Research Square Print

2022 Aug.

Solvant et solubilité

In Vitro:

DMSO : 25 mg/mL (45.03 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.8010 mL

9.0051 mL

18.0102 mL

5 mM

0.3602 mL

1.8010 mL

3.6020 mL

10 mM

0.1801 mL

0.9005 mL

1.8010 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Calculateur de molarité

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculateur de dilution

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (4.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (4.50 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocole

Kinase Assay^[3]

Macrophages are seeded (2×10⁶/well) in 12-well culture plates. AM-251 or SR144528 are added from 4 mM stock solutions prepared in DMSO, 1h prior to the addition of 7-ketocholesterol (7KC) from a 2 mg/mL ethanol stock solution. Controls are adjusted to receive equivalent volumes of DMSO and ethanol. After 16 h, caspase-3 activity is determined. All treatments are done in triplicate and the data presented as the mean RFLU/mg protein±SD^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[4]^[5]

Mice^[4]
A total of 246 mice weighing 17-48 g are used in these experiments. Following determination of baseline responding, mice receive a single i.p injection (5 mL/kg) of AMG9810 (3 mg/kg, n=5 per group), AM251 (3 mg/kg, n=5 per group), or vehicle (n=6 per group). I.p. injections are performed 30 min prior to i.pl. capsaicin or vehicle administration. Paw withdrawal latencies are assessed before and 10, 30, 60, 90 and 120 min after intradermal injection of capsaicin or vehicle. Paw withdrawal latencies are measured in duplicate in each paw at each time point, and are reported as the mean of the two duplicate determinations from each animal, averaged across subjects.
Rats^[5]
Male Wistar rats weighting 250-350 are used.The following agents are used: CB1 receptor agonist, Win-55212 (0.3, 1 and 5 mg/kg, i.p. ); CB1 receptor antagonist, AM251 (0.3, 1 and 5 mg/kg, i.p.); endocannabinoid breakdown inhibitor, URB-597 (0.03, 0.1 and 0.3 mg/kg, i.p.) in the study. Physiological saline (0.9% sodium chloride) is used as the vehicle. All drugs are prepared freshly and administered intraperitoneally (i.p.) in a volume of 0.1 mL per 10 g of body weight of the rats. All substances are dissolved in physiological saline and are administrated 30 min before elevated plus-maze test.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (284 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Instruction de manipulation (2659 KB)

Références

[1]. Bruno A, et al. Beyond radio-displacement techniques for identification of CB1 ligands: the first application of afluorescence-quenching assay. Sci Rep. 2014 Jan 20;4:3757. [Content Brief]

[2]. Sharir H, et al. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther. 2010 Jun;126(3):301-13. [Content Brief]

[3]. Thewke D, et al. AM-251 and SR144528 are acyl CoA:cholesterol acyltransferase inhibitors. Biochem Biophys Res Commun. 2009 Apr 3;381(2):181-6. [Content Brief]

[4]. Carey LM, et al. A pro-nociceptive phenotype unmasked in mice lacking fatty-acid amide hydrolase. Mol Pain. 2016 May 13;12. pii: 1744806916649192. [Content Brief]

[5]. Komaki A, et al. Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze. Basic Clin Neurosci. 2015 Jul;6(3):147-53. [Content Brief]

[6]. Jiang X, et al. Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats. Am J Physiol Renal Physiol. 2017 Mar 1;312(3):F482-F488. [Content Brief]

[7]. Sun L, et al. Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation. Eur J Pain. 2017 May;21(5):804-814. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.8010 mL	9.0051 mL	18.0102 mL	45.0256 mL
	5 mM	0.3602 mL	1.8010 mL	3.6020 mL	9.0051 mL
	10 mM	0.1801 mL	0.9005 mL	1.8010 mL	4.5026 mL
	15 mM	0.1201 mL	0.6003 mL	1.2007 mL	3.0017 mL
	20 mM	0.0901 mL	0.4503 mL	0.9005 mL	2.2513 mL
	25 mM	0.0720 mL	0.3602 mL	0.7204 mL	1.8010 mL
	30 mM	0.0600 mL	0.3002 mL	0.6003 mL	1.5009 mL
	40 mM	0.0450 mL	0.2251 mL	0.4503 mL	1.1256 mL

Keywords

AM251

26 Cited Publications

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AM251

GPCR/G Protein Compound Library

Neuronal Signaling Compound Library

Anti-Obesity Compound Library

Human Metabolite Library

Heterocyclic Compound Library

Pain-Related Compound Library

Membrane Protein-targeted Compound Library

Membrane Receptor-targeted Compound Library

Highly Selective Inhibitors Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Lactylation Compound Library

Publications Citing Use of MedChemExpress (MCE) AM251

Voir tous les produits spécifiques à Isoform Cannabinoid Receptor

Activité biologique

Chemical Information

Publications (26)

Solvant et solubilité

Protocole

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

AM251

GPCR/G Protein Compound Library

Neuronal Signaling Compound Library

Anti-Obesity Compound Library

Human Metabolite Library

Heterocyclic Compound Library

Pain-Related Compound Library

Membrane Protein-targeted Compound Library

Membrane Receptor-targeted Compound Library

Highly Selective Inhibitors Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Lactylation Compound Library

Publications Citing Use of MedChemExpress (MCE) AM251

Voir tous les produits spécifiques à Isoform Cannabinoid Receptor

Activité biologique

Chemical Information

Publications (26)

Solvant et solubilité

Protocole

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

AM251 Related Classifications

HY-15443 Related Classifications