MAGL Inhibitor

MGL-IN-1 is a potent and selective irreversible MGL (β-lactam-based monoacylglycerol lipase) inhibitor. MGL-IN-1 alleviates symptoms in a MS model in vivo and exhibits analgesic effects in an acute inflammatory pain model in vivo. MGL-IN-1 displays high membrane permeability and brain penetrant.

ML226 is a potent inhibitor of α/β hydrolase domain protein 11 (ABHD11), with in vitro and in situ IC₅₀ values ​​of 15 and 0.68 nM, respectively. ML226 is an inhibitor of protein palmitoylthioesterase lysophospholipase 1 (LYPLA1) and LYPLA2. ML226 can be used for research related to neurological diseases.

MAGL-IN-1 is a potent, selective, reversible and competitive inhibitor of MAGL, with an IC₅₀ of 80 nM. MAGL-IN-1 exhibits anti-proliferative effects against human breast, colorectal, and ovarian cancer cells. MAGL-IN-1 blocks MAGL in cell-based as well as in vivo assays.

PF-06795071 is a potent and selective covalent MAGL inhibitor with an IC₅₀ of 3 nM.

ABC34 is an inactive control compound of JJH260. ABC34 does not inhibit the fluorophosphonate reactivity or fatty acid esters of hydroxy fatty acid (FAHFA) hydrolysis activity of AIG1. ABC34 can inhibit both ABHD6 and PPT122.

AKU-005 is a FAAH and MAGL dual inhibitor with IC₅₀ values of 63, 389 nM for rat and human FAAH, respectively. AKU-005 has the potential for the research of trigeminal hyperalgesia.

JZP-MA-11 is a brain-penetrant positron emission tomography (PET) ligand targeting the brain endocannabinoid α/β-hydrolase domain 6 (ABHD6) enzyme. JZP-MA-11 selectively inhibits ABHD6 with an IC₅₀ value of 126 nM. [18F]JZP-MA-11 has the potential for preclinical evaluation targeting the brain ABHD6 in mice and nonhuman primate (NHP).

AA38-3 is a serine hydrolase (SH) inhibitor. AA38-3 can inhibit three SHs, ABHD6, ABHD11, and FAAH.

AM6701 is a potent FAAH/MAGL inhibitor (equipotent inhibitory IC₅₀: 1.2 nM) with neuroprotective effects.

N-Arachidonyl maleimide is a potent, irreversible inhibitor of monoacylglycerol lipase (MAGL) with an IC₅₀ value of 140 nM.

MAGL-IN-4 is an orally active, selective and reversible monoacylglycerol lipase (MAGL) inhibitor with an IC₅₀ of 6.2 nM. MAGL-IN-4 can penetrate the blood-brain barrier (BBB). MAGL-IN-4 enhances endocannabinoid signaling mostly by the increase in the level of 2-AG via selective MAGL inhibition in the brain.

Irafamdastat (BMS-986368) (Example 74) is a FAAH and MAGL inhibitor, with IC₅₀s ≤ 100 nM (human FAAH) and 100 nM-1 μM (human MAGL) respectively. Irafamdastat has antiepileptic effect.

JZP-430 is a potent, highly selective, irreversible inhibitor of α/β-hydrolase domain 6 (ABHD6) with an IC₅₀ of 44 nM, exhibits ~230-fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL).

JZP-361 is a potent, reversible and selective inhibitor of human recombinant MAGL (hMAGL) with an IC₅₀ of 46 nM. JZP-361 also shows antihistaminergic activities and can be used for asthma research.

LEI-106 is a dual ABHD6 and DAGL-α inhibitor, with a K_i of 0.8 μM for ABHD6, and an IC₅₀ of 18 nM and a K_i of 0.7 μM for DAGL-α. LEI-106 blocks the synthesis of 2-arachidonoylglycerol, reduces the level of endothelial cell-derived 2-arachidonoylglycerol, without altering the levels of cannabinoids and diacylglycerol. LEI-106 is applicable to research related to diet-induced obesity and metabolic syndrome.

KT185 is an orally-bioavailable, brain-penetrant and selective ABHD6 inhibitor, with an IC₅₀ 0.21 nM in Neuro2A cells.

WWL123 analogue-1 is an analogue of WWL123. WWL123 is a potent and selective ABHD6 inhibitor with an IC₅₀ of 430 nM. WWL123 crosses the blood-brain-barrier and inhibits ABHD6 in brain parenchyma. ABHD6 blockade by WWL123 exerts an antiepileptic effect in Pentylenetetrazole (PTZ)-induced epileptiform seizures and spontaneous seizures in R6/2 mice.

VDM11 is a potent and selective anandamide membrane transporter (AMT) inhibitor. VDM11 inhibits FAAH and MAGL and may act as an alternative FAAH substrate.

JZL 184 (Standard) is the analytical standard of JZL 184. This product is intended for research and analytical applications. JZL 184 is a potent, selective and irreversible MAGL inhibitor that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis in brain membranes (IC50 of 8 nM). JZL 184 displays >300-fold selectivity for MAGL over FAAH.

FAAH/MAGL-IN-3 (Compound 10) is an irreversible fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) dual inhibitor with IC₅₀ values of 179 and 759 nM against FAAH and MAGL, respectively. FAAH/MAGL-IN-3 shows low PAMPA (Parallel Artificial Membrane Permeability Assay) permeability.