Cannabinoid Receptors

PF-3845 is a potent, selective, and irreversible inhibitor of FAAH (Ki = 0.23 μM). It reduces inflammatory pain via a cannabinoid receptor-dependent mechanism.

GNE-049 is a highly potent and selective CBP inhibitor with an IC50 of 1.1 nM in TR-FRET assay. GNE-049 also inhibits BRET and BRD4(1) with IC50s of 12 nM and 4200 nM, respectively.

Voacamine is an indole alkaloid that acts as an antagonist of the cannabinoid receptor 1 (CB1) and also functions as a P-glycoprotein (P-gp) inhibitor. This compound enhances the efficacy of Doxorubicin by modulating P-gp activity, promoting apoptosis-independent autophagic cell death in human osteosarcoma cells. Additionally, Voacamine activates mitochondrial-associated apoptosis signaling pathways while inhibiting the PI3K/Akt/mTOR pathway, thus suppressing breast cancer progression. Moreover, it demonstrates oncogenic activity against colorectal cancer by inhibiting epidermal growth factor receptor (EGFR).

Yangonin is a selective cannabinoid receptor inhibitor that demonstrates affinity for the human recombinant CB1 receptor, with an IC50 value of 1.79 μM and a Ki of 0.72 μM. This compound is of significant interest for research applications aimed at understanding cannabinoid signaling and its implications in various physiological processes. Its modulation of CB1 receptor activity may provide insights into therapeutic strategies targeting cannabinoid-related pathways.

Hydroxy-PP-Me is a selective inhibitor of the cannabinoid receptor type 1 (CBR1) with an IC50 of 759 nM. It effectively inhibits serum starvation-induced apoptosis and enhances the cytotoxic effects of chemotherapeutic agents such as Daunorubicin and Arsenic Trioxide (As2O3) on tumor cells. Hydroxy-PP-Me is a valuable tool for cancer research, particularly in the study of leukemia and related malignancies.

Pregnenolone monosulfate sodium (3β-Hydroxy-5-pregnen-20-one monosulfate sodium) is a selective inhibitor of the cannabinoid CB1 receptor. This neurosteroid, a key precursor in steroid hormone synthesis, can mitigate the effects of tetrahydrocannabinol (THC) by blocking its action at CB1 receptors. Additionally, Pregnenolone monosulfate sodium serves as a TRPM3 channel activator and has been shown to weakly activate TRPM1 channels. Its unique properties make it a valuable tool for investigating cannabinoid signaling and neuroprotective strategies against cannabis-related effects.

Pregnenolone monosulfate (3β-Hydroxy-5-pregnen-20-one monosulfate) is a selective inhibitor of the cannabinoid CB1 receptor. By inhibiting the effects of tetrahydrocannabinol (THC) mediated through the CB1 receptors, it offers potential neuroprotective properties against cannabis intoxication. Additionally, Pregnenolone monosulfate serves as a TRPM3 channel activator and exhibits weak activation of TRPM1 channels, making it valuable for research in neuropharmacology and cannabinoid signaling pathways.

Leelamine is an orally active pyruvate dehydrogenase kinase (PDK) inhibitor, demonstrating an IC50 value of 9.5 μM. It effectively lowers blood glucose levels in diabetic mouse models. Additionally, Leelamine acts as a weak agonist of cannabinoid receptors CB1 and CB2. Its biological activity includes a reduction in mitotic activity and prostate-specific antigen expression, as well as the induction of apoptosis in cancer cells, making it a valuable tool for cancer research and metabolic studies.

2-Linoleoyl glycerol is a monoacylglycerol that serves as an antagonist and partial agonist at the cannabinoid receptor type 1 (CB1). It effectively modulates the activity of cannabinoids such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) by attenuating their effects without enhancing them. This compound has significant implications in cannabinoid research, particularly in studies focused on the endocannabinoid system and potential therapeutic targets for various conditions. Additionally, its potency can be influenced by the inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

ANEB-001 is an orally active inhibitor of the cannabinoid receptor type 1 (CB1). This compound is primarily utilized in research focused on acute cannabinoid intoxication, providing insights into the physiological effects and potential therapeutic approaches related to CB1 modulation. Its selective inhibition of CB1 makes it a valuable tool for studies investigating cannabinoid-related pathways and their implications in various biological contexts.

O-7460 is a selective inhibitor of diacylglycerol lipase alpha (DAGLα), exhibiting an IC50 value of 0.69 μM. This compound demonstrates selectivity against monoacylglycerol lipase (MAGL) and both human CB1 and CB2 cannabinoid receptors. O-7460 has been shown to effectively reduce elevated 2-arachidonoylglycerol (2-AG) levels associated with high-fat diet conditions, making it a valuable tool for studying endocannabinoid signaling and its implications in metabolic disorders.

Isopropyl dodec-11-enylfluorophosphonate (IDEFP) is a potent inhibitor of the central cannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH), exhibiting similar inhibitory activities with IC50 values around 2 nM. It serves as a valuable tool for investigating cannabinoid signaling pathways and lipid metabolism in various biological contexts. Researchers utilize IDEFP to explore the therapeutic potential of modulating endocannabinoid systems in pain, inflammation, and neuroprotection studies.

hBChE-IN-2 is a potent butyrylcholinesterase (BChE) inhibitor with an IC50 of 0.62 μM and functions as an agonist for cannabinoid receptor 2 (CB2R). This compound exhibits significant neuroprotective activities, making it a valuable tool in the study of neurodegenerative diseases and cannabinoid signaling pathways. Its dual action positions hBChE-IN-2 as an important reagent for research applications targeting cholinergic regulation and endocannabinoid modulation.

BI-5756 is a selective CETP inhibitor and cannabinoid receptor 1 (CB1) agonist. It promotes a significant increase in HDL-C levels while reducing LDL-C levels, thereby improving lipid profiles. Additionally, BI-5756 enhances the function of regulatory T cells and preserves T cell-mediated anti-tumor activity, exhibiting direct anti-proliferative effects on tumor cells. This compound also upregulates the expression of MHC I, MHC II, and CD80 on tumor cells and demonstrates protective effects in graft-versus-host disease. BI-5756 is applicable in research related to oncology, graft-versus-host disease, and metabolic disorders.

AM12814 is a potent and selective inhibitor of cannabinoid receptors CB1 and CB2, demonstrating Ki values of 0.7 nM and 3.4 nM, respectively. This compound effectively inhibits cAMP accumulation and promotes β-arrestin 2 recruitment, mimicking cannabimimetic effects. AM12814 is suitable for research applications related to neurological diseases, including studies on catalepsy.

CB2R/FAAH modulator-1 is a potent full agonist of the cannabinoid type 2 receptor (CB2R), exhibiting a binding affinity with a Ki of 14.8 nM for CB2R and 241.3 nM for CB1R. This compound also serves as an inhibitor of fatty acid amide hydrolase (FAAH), demonstrating an IC50 of 4 μM. CB2R/FAAH modulator-1 is effective in modulating cytokine production by decreasing pro-inflammatory cytokines while enhancing anti-inflammatory cytokine levels, making it valuable for research in inflammation and pain modulation.

N-(3-Hydroxyphenyl)-arachidonoyl amide is an anandamide transport inhibitor, exhibiting an IC50 of 21.3 μM. This compound serves as a valuable tool in understanding endocannabinoid signaling and lipid metabolism. It can be utilized in research applications focusing on cannabinoid receptors and the modulation of neuronal activity.

CB1-IN-2 is a selective CB1 receptor inhibitor, characterized by an IC50 of 0.644 μM. This compound effectively penetrates the blood-brain barrier, making it suitable for studies exploring its potential central nervous system effects. CB1-IN-2 can be applied in research focused on cannabinoid receptor modulation and its implications in various neurological and psychological conditions.

LEI105 is a selective and reversible dual inhibitor of diacylglycerol lipase (DAGL)-α and DAGL-β. This compound effectively decreases levels of 2-arachidonoylglycerol in Neuro2A cells, demonstrating its potential to modulate endocannabinoid signaling. Research applications include investigations into the mechanisms underlying obesity, metabolic disorders, and neuroinflammation, as well as studies of cannabinoid receptor-mediated synaptic plasticity in mouse hippocampal slices.

Cannabidiorcol (CBDO) is an inhibitor of transient receptor potential (TRP) channels. This compound, structurally related to cannabidiol with a shortened pentyl side chain, exhibits anti-inflammatory properties while displaying low affinity for cannabinoid receptors. Research applications include investigations into its potential role in modulating inflammation and exploring its effects on tumorigenesis at elevated concentrations.

OMDM-5 is a selective anandamide cellular uptake (ACU) inhibitor, exhibiting a Ki of 4.8 μM. In addition, OMDM-5 demonstrates potent activity as a vanilloid receptor type 1 (VR1, TRPV1) agonist, with an EC50 of 75 nM. This compound also shows weak activity as a cannabinoid receptor type 1 (CB1) ligand, with a Ki of 4.9 μM. Its properties make OMDM-5 useful for studies involving pain modulation and endocannabinoid signaling pathways.

OMDM169 is a selective inhibitor of monoacylglycerol lipase (MAGL), effectively increasing the levels of 2-arachidonoylglycerol (2-AG) in biological systems. This compound demonstrates significant analgesic properties through the indirect activation of cannabinoid receptors. OMDM169 exhibits an effective concentration of 0.13 μM, making it a valuable tool for research focused on pain modulation and cannabinoid receptor signaling pathways.

3-Decyl-5,5'-diphenyl-2-thioxo-4-imidazolidinone is a potent inhibitor of fatty acid amide hydrolase (FAAH) with a pI50 of 5.89. This compound exhibits significant activity against endocannabinoids and lipid mediators, making it relevant for studies in pain management, inflammation, and cannabinoid signaling pathways. Its limited affinity for cannabinoid receptors CB(1) and CB(2) allows for targeted research into FAAH-related physiological processes without direct receptor modulation.

Olivetol is a naturally occurring phenol that functions as a competitive inhibitor of cytochrome P450 enzymes, specifically CYP2C19 and CYP2D6, with IC50 values of 15.3 μM and 7.21 μM, respectively. Additionally, olivetol has demonstrated inhibitory activity against cannabinoid receptors CB1 and CB2. This compound is useful in research related to drug metabolism, pharmacokinetics, and the modulation of cannabinoid signaling pathways.