Buy JZL 184 online
Is a useful tool for studying the effects of endogenous 2-AG signaling. Buy JZL 184 online displays time-dependent inhibition of MAGL and exhibits >300-fold selectivity for MAGL over FAAH in vitro. JZL 184 does not interact with CB1 or CB2 receptors and does not inhibit the 2-AG biosynthetic enzymes diacylglycerol lipase-αand diacylglycerol lipase-β, or the arachidonic acid–mobilizing enzyme cytosolic phospholipase A2 group IVA.
2.What is the dosage of JZL 184 ?
Add solvents to the product individually and in order:30% PEG400+0.5% Tween80+5% Propylene glycol
For best results, use promptly after mixing.
Stability and Solubility Advice:
Some solutions can be difficult to obtain and can be encouraged by rapid stirring, sonication or gentle warming (in a 45-60°C water bath). Information concerning product stability, particularly in solution, has rarely been reported and in most cases we can only offer a general guide. Our standard recommendations are: SOLIDS: Provided storage is as stated on the product label and the vial is kept tightly sealed, the product can be stored for up to 6 months from date of receipt. SOLUTIONS: We recommend that stock solutions, once prepared, are stored aliquoted in tightly sealed vials at -20°C or below and used within 1 month. Wherever possible solutions
should be made up and used on the same day.
3.How JZL 184 works?
JZL 184 prevents HIV-1 gp120-induced synapse loss by altering endocannabinoid signaling.
Monoacylglycerol lipase (MGL) hydrolyzes 2-arachidonoylglycerol to arachidonic acidand glycerol. Inhibition of MGL may attenuate neuroinflammation by enhancing endocannabinoid signaling and decreasing prostaglandin (PG) production. Almost half of HIV infected individuals are afflicted with HIV-associated neurocognitive disorder (HAND), a neuroinflammatory disease in which cognitive decline correlates with synapse loss. HIV infected cells shed the envelope protein gp120 which is a potent neurotoxin that induces synapse loss. Here, we tested whether inhibition of MGL, usingthe selective inhibitor JZL 184, would prevent synapse loss induced by gp120.
The number of synapses between rat hippocampal neurons in culture was quantified by imaging clusters of aGFP-tagged antibody-like protein that selectively binds to the postsynaptic scaffolding protein, PSD95. JZL 184 completely blocked gp120-induced synapse loss. Inhibition of MGL decreased gp120-induced interleukin-1β (IL-1β) production and subsequent potentiation of NMDA receptor-mediated calcium influx. JZL 184-mediated protection of synapses was reversed by a selective cannabinoid type 2receptor (CB2R) inverse agonist/antagonist. JZL 184 also reduced gp120-induced prostaglandin E2 (PGE2) production; PG signaling was required for gp120-induced IL-1β expression and synapse loss. Inhibition of MGL prevented gp120-induced synapse loss by activating CB2R resulting in decreased production of the inflammatory cytokine IL-1β. Because PG signaling was required for gp120-induced synapse loss, JZL 184-induced decreases in PGE2 levels may also protect synapses.
MGL presentsa promising target for preventingsynapse loss in neuroinflammatory conditions such as HAND. Potent and selective MAGL inhibitor. Blocks hydrolysis of the endocannabinoid 2-arachidonyl glycerol (2-AG) in vivo in the mouse brain (IC50 = 8 nM). Potentiates depolarization-induced suppression of excitability in cerebellar Purkinje neurons. Exhibits>300-fold selectivity for MAGL over FAAH in vitro. Attenuates nociception in neuropathic and inflammatory pain models. Also reduces free fatty acid levels in primary tumors.
4.Warning:
4.1 Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these willbeuseable for up to one month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
4.2 Please note that tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due toslight batch-to-batch variations.
4.3 Exposure controls and personal protection: In case of skin contact, eye contact,inhaled,swallowed,consult a doctor if any discomfort.
5.JZL 184 Raw Powder:
Min order 10 grams.
The inquiry on normal quantity (Within 1kg) can be sent out in 12 hours after payment.
For larger order can be sent out in 3 working days after payment.
6.JZL 184 Raw Powder Recipes:
To inquiry our Customer Representitive (CSR) for details, for your reference.
7.JZL 184 Marketing:
To be provided in the coming future.
8.Side Effects?
JZL 184 produced a rapid and sustained blockade of brain 2-AG hydrolase activity in mice, resulting in eight-fold elevations in endogenous 2-AG levels that are maintained for at least 8 h. JZL 184-treated mice showed a wide array of CB1-dependent behavioral effects, including analgesia, hypomotility and hypothermia, that suggest abroad role for 2-AG–mediated endocannabinoid signaling throughout the mammalian nervous system.
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