CB2 (cannabinoid receptor type 2)

JWH-133 is a synthetic cannabinoid and a potent & selective agonist of the CB2 receptor with a Ki of 3.4nM and selectivity of ~ 200x for CB2 over CB1 receptors. It was discovered by and named after, John W. Huffman. JWH-133 is responsible for preventing the inflammation caused by Amyloid beta proteins involved in Alzheimers Disease, in addition to preventing cognitive impairment and loss of neuronal markers. This anti-inflammatory action is induced through agonist action at cannabinoid receptors, which prevents microglial activation that elicits the inflammation. Additionally, cannabinoids completely abolish neurotoxicity related to microglia activation in rat models. It may also have anticancer activities.

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Kinase Assay: JWH-133 evoked a concentration-related inhibition (10 nM-5 microM) of LPS/IFN-gamma induced IL-12p40 release. The effect of JWH-133 (100 nM) was significantly blocked by the CB2 antagonist SR-144528 (1 microM). Macrophages infected with TMEV increased IL-12p40 production and activation of CB2 receptors by JWH-133 (100 nM) inhibited it. The inhibitory effect of JWH-133 (100 nM) on IL-12p40 production may involve extracellular-regulated kinase (ERK1/2) signaling: (i) JWH-133 induced a greater and sustained activation of ERK1/2 kinase in comparison with the level of activation observed following LPS; (ii) the inhibition of ERK1/2 by the specific inhibitor PD98059 increased LPS-induced IL-12p40 production in the presence or absence of JWH-133 suggesting a negative regulation of ERK pathway on IL-12p40 biosynthesis.

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Cell Assay: Activation of CB2 receptors by JWH-133 (10 nM-5 microM) enhanced IL-10 release by LPS/IFN-gamma-activated macrophages and addition of SR144558 (1 microM) totally blocked the effect of JWH (100 nM). 5 Inhibition of ERK by PD98059 significantly suppressed IL-10 production by LPS-activated macrophages. Endogenous IL-10 plays a modulatory role in IL-12 production. Blocking IL-10 with neutralizing antibody resulted in increased IL-12p40 secretion by LPS-activated macrophages in the absence or presence of JWH-133. In contrast, the addition of exogenous mIL-10 reduced the secretion of IL-12p40 in response to LPS.

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Exhibits a Ki of 3.4 nM for the CB2 receptor, demonstrating approximately 200-fold selectivity over the CB1 receptor. JWH-133 behaves as a CB2 receptor full agonist in both spleen and hCB2-CHO cells in both [35S]GTPγS and cAMP assays.

Exerts toxic effects on neuroblastoma SH-SY5Y cells, reduces spasticity in a murine model of multiple sclerosis, suppresses the viability and migration of prostate cancer cell lines, and improves cognitive impairment in Alzheimer's disease models. Systemic administration significantly and dose-dependently inhibits intravenous cocaine self-administration.

Receptor binding assays were performed to determine Ki values for CB2 and CB1 using standard radioligand displacement techniques with membranes from cells expressing the respective receptors. The compound was characterized as a full agonist in both [35S]GTPγS and cAMP assays.

Neuroblastoma SH-SY5Y cells and prostate cancer cell lines (LNCaP, DU-145, PC3) were treated with JWH-133 to assess cell viability via MTT assay, colony formation, and wound-healing assays. JWH-133 modulates MAPK pathways including ERK1/2, JNK, and p38 MAPK, and suppresses NF-κB activation.

Oral or systemic administration of JWH-133 in animal models has been shown to improve cognitive impairment in Alzheimer's disease models, attenuate behavior deficits in Parkinson's disease models, and reduce mammary gland tumors in transgenic mice. Intraperitoneal administration at 10-20 mg/kg produces effects lasting up to 24 hours.

Pharmacol Rep.2017 Dec;69(6):1131-1139.

JWH-133 is a dibenzopyran compound, a derivative of δ(9)-tetrahydrocannabinol, lacking a hydroxyl group and with the pentyl group at the 3-position replaced by a 1,1-dimethylbutyl group. It is a potent and highly selective CB2 receptor agonist. JWH-133 possesses a variety of pharmacological activities, including as a CB2 receptor agonist, antitumor drug, vasodilator, anti-inflammatory drug, apoptosis inhibitor, analgesic, and opioid analgesic. It belongs to the dibenzopyran class, organoheterocyclic compounds, and benzochromene class.

C22H32O

312.49

312.245

259869-55-1

6918505

Typically exists as solid at room temperature

6.375

9.23

0

1

3

23

459

2

CC(C1=CC2=C(C=C1)[C@@](CC(C)=CC3)([H])[C@]3([H])C(C)(C)O2)(C)CCC

YSBFLLZNALVODA-RBUKOAKNSA-N

InChI=1S/C22H32O/c1-7-12-21(3,4)16-9-10-17-18-13-15(2)8-11-19(18)22(5,6)23-20(17)14-16/h8-10,14,18-19H,7,11-13H2,1-6H3/t18-,19+/m0/s1

(6aR,10aR)-6,6,9-trimethyl-3-(2-methylpentan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 10 mM
Water: 1 mg/mL (Insoluble)
Ethanol: 1 mg/mL

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)