6-Iodopravadoline (AM630)

Catalog No.S8033 Batch:S803301

Technical Data

Formula

C₂₃H₂₅IN₂O₃

Molecular Weight

504.36

CAS No.

164178-33-0

Solubility (25°C)*

In vitro

DMSO

50 mg/mL (99.13 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5% DMSO 1 95% Corn oil	0.4mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	2.5mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

6-Iodopravadoline (AM630) is a selective cannabinoid CB2 receptor antagonist with Ki of 31.2 nM.

Targets

CB2 receptor ^[1]
(Cell-free assay)

31.2 nM(Ki)

In vitro

AM630 is a CB2 cannabinoid receptor ligand with K_i of 31.2 nM and a CB2 /CB1 affinity ratio of 165. AM630 inhibits [³⁵ S]-GTPγS binding to CB2 receptor membranes (EC50=76.6 nM), enhances forskolin-stimulated cyclic AMP production in CB2-transfected cells (5.2 fold by 1 μM ), and antagonizes the inhibition of forskolin-stimulated cyclic AMP production in this cell line induced by CP55940. AM630 (10 μM) inhibits forskolin-stimulated cyclic AMP production In CB1-transfected cells by 45.9%. ^[1] AM630 behaves as a competitive antagonist of △⁹-THC, CP 55,940, WIN 55212-2, anandamide and (R)-(+)-arachidonyl-l’-hydroxy-2’-propylamide (AM356) in mouse isolated vas deferens with K_d of 14.0, 17.3, 36.5, 278.8, and 85.9 nM, respectively. ^[2] AM630 ( 10 μM) activates a robust Ca²⁺ accumulation in a subset (35- 40%) of TG neurons, and with EC50 of 15.6 μM. AM630 are able to generate currents in TG sensory neurons with the activation threshold of 1 μM. AM630 responses are mediated by the TRPA1 channel in a majority of TG small-to-medium sensory neurons, which is modulated by TRPV1. Pre-treatment with AM630 (25 μM) is able to inhibits the Capsaicin (CAP) effects, mustard oil (MO) and WIN 55,212-2 (WIN) TRPA1 mediated responses. ^[3] AM630 (100 nM) effectively inhibits osteoclastogenesis in culture with RANKL in the presence and absence of Ti particles, as reducing the number of tartrate-resistant acid phosphatase-positive cells by more than 50%. AM630 (100 nM) inhibits mRNA expression of RANK and cathepsin K in RAW cells stimulated by Ti particles and RANKL. AM630 (100 nM) reduces protein expression of interleukin-1β and tumor necrosis factor-α in RAW cells cultured with Ti particles. AM630 has no toxic effect on RAW cells. ^[4]

In vivo

AM630 (30 μg) injection are not able to induce nociceptive behaviors or thermal hyperalgesia in hind paw of WT mice, but significantly attenuate CAP-induced thermal hyperalgesia. AM630 (30 μg) is able to reverse WIN inhibition CAP-induced thermal hyperalgesia. AM630 exerts its peripheral effects by not only inhibiting CB1 and CB2, but also activating TRPA1 channels and subsequently desensitizing TRPA1 as well as TRPV1 channels. ^[3]

Biological Activity

Description

6-Iodopravadoline (AM630) is a selective cannabinoid CB2 receptor antagonist with Ki of 31.2 nM.

Targets

CB2 receptor ^[1]
(Cell-free assay)

31.2 nM(Ki)

In vitro

AM630 behaves as a low-potency neutral competitive antagonist in AM630-pre-incubated cells, a low-potency agonist in SR144528-pre-incubated cells, and a much higher-potency inverse agonist/antagonist in vehicle-pre-incubated cells. AM630 is a protean ligand that can target a constitutively active form of the hCB2 receptor with low affinity to produce agonism or neutral antagonism and a constitutively inactive form of this receptor with much higher affinity to produce inverse agonism.^[2]

In vivo

Chronic AM630 treatment is anxiolytic in light-dark box (LDB) and elevated plus maze (EPM) tests. Chronic AM630 treatment increases gene and reduces protein expression of CB2 receptors, GABAAα2 and GABAAγ2 in cortex and amygdala. In addition, chronic AM630 administration decreases the anxiety of DBA/2 mice in the LDB test. The efficacy of AM630 in reducing the anxiety of the spontaneously anxious DBA/2 strain of mice strengthens the potential of the CB2 receptor as a new target in the treatment of anxiety-related disorders.^[1]

Protocol (from reference)

Cell Assay:^{^[2]}	Cell lines CHO cells Concentrations 10 μM Incubation Time 24 h Method Binding assays with [3H]-CP55940 or [35S]-GTPγS are performed with hCB2 CHO cell membranes. The hCB2 CHO cells are pre-incubated in complete medium with 10 μM AM630 or vehicle (dimethyl sulphoxide) for up to 24 h and then subjected to intense washing. For membrane preparation, cells are removed from flasks by scraping, centrifuged at 489× g and then frozen as a pellet at −20°C until required. Before use in a radioligand binding assay, cells are defrosted and diluted in Tris binding buffer (radioligand displacement assay) or GTPγS binding buffer ([35S]-GTPγS binding assay).
Animal Study:^{^[1]}	Animal Models male Swiss ICR mice, DBA/2 Ola Hs mice Dosages 1 mg/kg, 2 mg/kg, 3 mg/kg Administration IP

Cell Assay:^{^[2]}

Cell lines
CHO cells
Concentrations
10 μM
Incubation Time
24 h
Method
Binding assays with [3H]-CP55940 or [35S]-GTPγS are performed with hCB2 CHO cell membranes. The hCB2 CHO cells are pre-incubated in complete medium with 10 μM AM630 or vehicle (dimethyl sulphoxide) for up to 24 h and then subjected to intense washing. For membrane preparation, cells are removed from flasks by scraping, centrifuged at 489× g and then frozen as a pellet at −20°C until required. Before use in a radioligand binding assay, cells are defrosted and diluted in Tris binding buffer (radioligand displacement assay) or GTPγS binding buffer ([35S]-GTPγS binding assay).

Animal Study:^{^[1]}

Animal Models
male Swiss ICR mice, DBA/2 Ola Hs mice
Dosages
1 mg/kg, 2 mg/kg, 3 mg/kg
Administration
IP

References

Selleck's 6-Iodopravadoline (AM630) has been cited by 2 publications

CB2R activation ameliorates late adolescent chronic alcohol exposure-induced anxiety-like behaviors during withdrawal by preventing morphological changes and suppressing NLRP3 inflammasome activation in prefrontal cortex microglia in mice [ Brain Behav Immun, 2023, 110:60-79]	PubMed: 36754245
Wwl70-induced ABHD6 inhibition attenuates memory deficits and pathological phenotypes in APPswe/PS1dE9 mice [ Pharmacol Res, 2023, 194:106864]	PubMed: 37480972

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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