JZL184 - CAS 1101854-58-3
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Not Intended for Therapeutic Use. For research use only.
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JZL 184 is the first selective inhibitor of monoacylglycerol lipase (MAGL) with IC50 of 8 nM.
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1.Lack of hippocampal CB1 receptor desensitization by Δ9-tetrahydrocannabinol in aged mice and by low doses of JZL 184.
Feliszek M1, Bindila L2, Lutz B2, Zimmer A3, Bilkei-Gorzo A3, Schlicker E4. Naunyn Schmiedebergs Arch Pharmacol. 2016 Mar 17. [Epub ahead of print]
Activation of cannabinoid CB1 receptors may offer new therapeutic strategies, but the efficiency of CB1 receptor agonists may be impaired by tolerance development upon prolonged administration. We compared the influence of repeated administration of Δ9-tetrahydrocannabinol (THC) 10 mg/kg on the motility and on basal and CB1 receptor-stimulated 35S-GTPγS binding of adolescent and aged mice. Moreover, we determined the influence of JZL 184 (which inhibits the 2-arachidonoylglycerol, 2-AG, degrading enzyme monoacylglycerol lipase, MAGL) on 35S-GTPγS binding and 2-AG levels of young adult mice. Mouse motility was tested in the open field. 35S-GTPγS binding was studied in hippocampal membranes. THC and CP 55,940 were used as cannabinoid agonists in the behavioural and biochemical studies, respectively. 2-AG levels were quantified by liquid chromatography-multiple reaction monitoring. The THC (10 mg/kg)-induced hypomotility was stronger in untreated than in THC-pretreated adolescent mice but similar in both treatment groups of aged mice.
2.Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells.
Ma M1, Bai J1, Ling Y1, Chang W1, Xie G1, Li R1, Wang G1, Tao K1. Mol Med Rep. 2016 Mar;13(3):2850-6. doi: 10.3892/mmr.2016.4829. Epub 2016 Jan 29.
Monoacylglycerol lipase (MAGL) is involved in the degradation of triacylglycerol. Previous studies have demonstrated that MAGL regulates tumor growth and metastasis via fatty acid networks, and is associated with colorectal cancer. JZL184 is a MAGL inhibitor, which in the present study was administered to colorectal cancer cell lines, resulting in decreased tumor proliferation, increased apoptosis and increased tumor cell sensitivity to 5-fluorouracil. B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) are key proteins in apoptosis. The expression levels of Bcl‑2/Bax were determined in colorectal cancer cell lines following JZL184 administration, and it was observed that the mRNA and protein expression levels of Bcl‑2 were decreased, whereas the expression levels of Bax were increased. These results indicated that JZL184 may induce tumor cell apoptosis by regulating the expression of Bcl‑2 and Bax. Epithelial-mesenchymal transition (EMT) is closely associated with metastasis.
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CAS 1101854-58-3 JZL184

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