CB2 Agonist

Bay 59-3074 is a selective cannabinoid CB₁/CB₂ receptor partial agonist with K_i values of 48.3 and 45.5 nM at human CB₁ and CB₂ receptors, respectively. Bay 59-3074 has analgesic properties.

Noladin ether is a potent and selective agonist of cannabinoid CB₁ receptor, with a K_i of 21.2 nM. Noladin ether can cause hypothermia, intestinal immobility, and mild antinociception.

Tedalinab (GRC-10693) is a potent, orally active, and selective cannabinoid receptor 2 (CB2) agonist. Tedalinab has >4700-fold functional selectivity for CB2 over CB1. Tedalinab has potential for neuropathic pain and osteoarthritis treatment.

CB2R/FAAH modulator-3 (compound 27) is a dual targeting modulator that acts as a CB2R agonist and FAAH inhibitor. The K_i values for CB2R/FAAH modulator-3 are 20.1 and 67.6 nM for CB2R and CB1R, respectively, and the IC₅₀ value for FAAH is 3.4 μM. CB2R/FAAH modulator-3 can be used in studies related to cancer, deleterious inflammatory cascades occurring in neurodegenerative diseases, and COVID-19 infection.

Vicasinabin (RG7774) is an orally active, selective, and full CB2R agonist, with EC₅₀ values of 2.81 nM and 2.60 nM for human CB2R and mouse CB2R, respectively. Vicasinabin inhibits inflammation, reduces leukocyte adhesion and decreases vascular permeability by selectively activating CB2R. Vicasinabin can be used in the researches for diabetic retinopathy, uveitis and laser-induced choroidal neovascularization.

CB2 receptor agonist 9 (Compound 33) is an orally active agonist for cannabinoid receptor 2 (CB2 receptor) with an EC₅₀ of 16.2 nM. CB2 receptor agonist 9 inhibits the expression of TNF-α, IL-1β and IL-6, exhibits anti-inflammatory efficacy in DDS (HY-116282)-induced mouse acute colitis model.

(±)5(6)-EET Ethanolamide is a metabolite of Anandamide (HY-10863) generated via oxidation by cytochrome P450 enzymes. (±)5(6)-EET Ethanolamide is also a selective cannabinoid receptor 2 (CB2) agonist. (±)5(6)-EET Ethanolamide has K_i values of 11.4 μM and 8.9 nM for human CB1 and CB2, respectively . (±)5(6)-EET Ethanolamide can be used in research on immunomodulation and neuroinflammation.

TRPM8 antagonist 4 is a CB2R partial agonist (EC₅₀=54.2 nM, K_i=3.2 μM) and TRPM8 antagonists (IC₅₀=42.3 nM) with high functional selectivity and good physicochemical properties. TRPM8 antagonist 4 has significant anti-inflammatory and analgesic effects and good safety, reduces the mRNA expression of TNF-α, IL-6, and IL-1β.

CB2 receptor agonist 8 (Compound 17) is an agonist for cannabinoid receptor 2 (CB2 receptor). CB2 receptor agonist 8 exhibits cytotoxicity in cells U87, RPMI 8226, HL-60, and L929 with IC₅₀s of 91.03, 16.29, 23.51 and 564.6 μM, respectively. CB2 receptor agonist 8 activates caspase 3/7, increases the expressions of pro-apoptotic genes BAX, BAD, BIM and tumor suppressor genes p53, and induces apoptosis in U87. CB2 receptor agonist 8 inhibits the migration of U87.

Neuroprotective agent 15 (Compound 3e) is a neuroprotective agent. Neuroprotective agent 15 is a selective butyrylcholinesterase (BChE) inhibitor, with IC₅₀ values of 2.6 and 114.3 μM for BChE and AChE respectively. Neuroprotective agent 15 has cannabinoid CB2 receptor (CB2 receptor) agonistic activity. Neuroprotective agent 15 can reduce cell death, LDH release and Caspase-3/7 activity, and inhibit apoptosis. Neuroprotective agent 15 can reduce the formation of superoxide free radicals, maintain cell morphology, and significantly lower oxidative stress levels. Neuroprotective agent 15 can be used in the research of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

hBChE-IN-2 (compound 15d) is a butyrylcholinesterase (BChE) inhibitor (IC₅₀ of 0.62 μM) and a cannabinoid receptor 2 (CB2R) agonist. hBChE-IN-2 has neuroprotection activities.

BAY 38-7271 is selective and highly potent and cannabinoid CB₁/CB₂ receptor agonist, with K_is of 1.85 nM and 5.96 nM for recombinant human CB₁ receptor and CB₂ receptor, respectively. BAY 38-7271 has strong neuroprotective properties.

CB2R agonist 3 is an agonist of cannabinoid receptor 2 (CB2R), with EC₅₀ of 0.37μM that plays an important role in immune system.

SMM-189 is  a potent and selective cannabinoid receptor 2 (CB2) inverse agonist. SMM-189 plays an important role in neurodegenerative disorders and traumatic brain injury research.

ISAM-CG557 is a selective CB2R agonist, with a K_i of 54.6 nM. ISAM-CG557 reduces intracellular ROS levels and caspase activity. ISAM-CG557 exhibits significant MAPK bias and moderate G-protein bias, with CB2R EC₅₀s of 0.60 nM (cAMP), 60.9 nM (β-arrestin) and 0.03 nM (MAPK). ISAM-CG557 exerts potent anti-inflammatory effects by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines in cells. ISAM-CG557 can be used for the study of neuroinflammatory and neurodegenerative disorders.

MDA7 is the selective agonist for cannabinoid receptor 2 with EC₅₀ of 128 nM and 67.4 nM in human CB2 receptor and rat CB2 receptor. MDA7 exhibits good affinity to human CB2 receptor and rat CB2 receptor with K_i of 422 nM and 238 nM. MDA7 exhibits analgesic activity in rats models.

MN-25 (compound 4a) is an orally active indolpyridone that serves as a novel cannabinoid ligand. MN-25 has K_i of 245 nM and 11 nM for CB1 and CB2. MN-25 has CB2 agonist activity and inhibits TNF-R release in human peripheral blood mononuclear cells in vitro with an IC₅₀ of 33 μM. MN-25 shows efficacy in a mouse acute inflammation model at oral doses up to 50 mg/kg^>[1].

TRPM8 antagonist 4 prodrug (Compound 8b) is an orally active CB₂R agonist (EC₅₀: 51.2 nM) and a weak TRPM8 antagonist. TRPM8 antagonist 4 prodrug is a prodrug of TRPM8 antagonist 4 (HY-174825). TRPM8 antagonist 4 prodrug exhibits anti-inflammatory and analgesic activities and can be used in the research of inflammation-related pain disorders.

L-759656 is a selective cannabinoid CB2 receptor agonist, with the K_i of 11.8 nM for the human CB2 receptor. L-759656 potently inhibits Forskolin (HY-15371)-stimulated cyclic AMP production in Chinese Hamster Ovary (CHO) cells, with an EC₅₀ of 3.1 nM. L-759656 can be used for the study of immune-related diseases and inflammatory diseases.

VU6077967 is a selective cannabinoid receptor 2 (CB2) agonist with an EC₅₀ of 8.6 nM for rCB2. VU6077967 can be used for the research of neurological disease, suah as Alzheimer’s disease.