Last update 01 Nov 2024

MAGL

Last update 01 Nov 2024

Basic Info

Synonyms

HU-K5, Lysophospholipase homolog, Lysophospholipase-like

+ [6]

Introduction

Converts monoacylglycerides to free fatty acids and glycerol (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth (PubMed:20079333).

Drugs associated with MAGL

ABX-1431

Target

MAGL

Mechanism

MAGL inhibitors

Active Org.

H. Lundbeck A/S

Originator Org.

Abide Therapeutics, Inc.

Active Indication

Stress Disorders, Post-Traumatic

Inactive Indication

Diabetic peripheral neuropathic pain [+13]

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ABX-1488

Target

MAGL

Mechanism

MAGL modulators [+1]

Active Org.

Abide Therapeutics, Inc.

Originator Org.

Abide Therapeutics, Inc.

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Lu-AG06474

Target

MAGL

Mechanism

MAGL inhibitors

Active Org.

H. Lundbeck A/S

Originator Org.

H. Lundbeck A/S

Active Indication

Pain

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with MAGL

NCT06077786 / CompletedPhase 1

An Interventional Randomized, Double-blind, Placebo and Active Comparator-controlled, Four-way Crossover Trial Investigating the Analgesic Properties of a Single Oral Dose of Lu AG06474 in Healthy Participants

The main goal of this trial is to learn about the effect of Lu AG06474 on a battery of Evoked Pain Tests when a single dose is given to healthy adult participants. The effects of Lu AG06474 will be compared with 2 approved pain-relieving medications (ibuprofen and pregabalin) and with a placebo (a treatment that looks like the trial treatment but does not have any medicine in it). Each participant will receive 1 dose of each of these treatments during the trial (Lu AG06474, ibuprofen, pregabalin, and placebo), with 1 week between treatments. All treatments will be taken orally (by mouth), either as a liquid or a capsule.

Start Date13 Oct 2023

Sponsor / Collaborator

H. Lundbeck A/S

NCT05943327 / RecruitingPhase 1

Interventional, Randomized, Double-blind, Sequential Cohort, Placebo-controlled, Multiple-dose Trial Investigating the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Properties of Lu AG06474 in Healthy Young Men and Women, With an Open-label, Cross-over, Single-dose Part Investigating the Relative Bioavailability of a Capsule Formulation

The purpose of this study is to investigate the safety of multiple oral doses of Lu AG06474, how well the doses are tolerated, and what the body does to the drug after administering it to healthy young participants. This study also aims to compare how the body absorbs and uses Lu AG06474 when it is given in capsule form versus when it is given as an oral solution.

Start Date28 Jun 2023

Sponsor / Collaborator

H. Lundbeck A/S

NCT05219838 / CompletedPhase 1

Interventional , Open-label, Positron Emission Tomography (PET) Study With [18F]-T-401 Investigating MAGL Enzyme Occupancy After Multiple Oral Doses of Lu AG06466

This study is being done to learn about the binding of Lu AG06466 and its major breakdown product (Lu AG06988) in the brain of healthy men having received multiple doses of Lu AG06466. As the binding will result in inhibition of an enzyme in the endocannabinoid system called monoacylglycerol lipase (MAGL), the effects on this system will be evaluated both in the blood and cerebrospinal fluid and compared to the binding in the brain.

Start Date18 Jan 2022

Sponsor / Collaborator

H. Lundbeck A/S

100 Clinical Results associated with MAGL

100 Translational Medicine associated with MAGL

0 Patents (Medical) associated with MAGL

1,633

Literatures (Medical) associated with MAGL

31 Dec 2024·Journal of Enzyme Inhibition and Medicinal Chemistry

Watermelon: setup and validation of an in silico fragment-based approach

Article

Author: Macchia, Marco ; Gado, Francesca ; Di Stefano, Miriana ; Galati, Salvatore ; Granchi, Carlotta ; Poli, Giulio ; Giordano, Antonio ; Piazza, Lisa ; Tuccinardi, Tiziano

We present a new computational approach, named Watermelon, designed for the development of pharmacophore models based on receptor structures. The methodology involves the sampling of potential hotspots for ligand interactions within a protein target's binding site, utilising molecular fragments as probes. By employing docking and molecular dynamics (MD) simulations, the most significant interactions formed by these probes within distinct regions of the binding site are identified. These interactions are subsequently transformed into pharmacophore features that delineates key anchoring sites for potential ligands. The reliability of the approach was experimentally validated using the monoacylglycerol lipase (MAGL) enzyme. The generated pharmacophore model captured features representing ligand-MAGL interactions observed in various X-ray co-crystal structures and was employed to screen a database of commercially available compounds, in combination with consensus docking and MD simulations. The screening successfully identified two new MAGL inhibitors with micromolar potency, thus confirming the reliability of the Watermelon approach.

01 Dec 2024·Cellular and Molecular Life Sciences

MAGL blockade alleviates steroid-induced femoral head osteonecrosis by reprogramming BMSC fate in rat

Article

Author: Wu, Lunan ; Yang, Ning ; Li, Xuefeng ; Wang, Wenzhi ; Wang, Zhen ; Zhu, Chen ; Li, Meng ; Xu, Yaozeng ; Geng, Dechun

The leading cause of steroid-induced femoral head osteonecrosis (ONFH) is the imbalance of bone homeostasis. Bone marrow-derived mesenchymal stem cell (BMSC) differentiation and fate are closely associated with bone homeostasis imbalance. Blocking monoacylglycerol lipase (MAGL) could effectively ameliorate ONFH by mitigating oxidative stress and apoptosis in BMSCs induced by glucocorticoids (GC). Nevertheless, whether MAGL inhibition can modulate the balance during BMSC differentiation, and therefore improve ONFH, remains elusive. Our study indicates that MAGL inhibition can effectively rescue the enhanced BMSC adipogenic differentiation caused by GC and promote their differentiation toward osteogenic lineages. Cannabinoid receptor 2 (CB2) is the direct downstream target of MAGL in BMSCs, rather than cannabinoid receptor 1(CB1). Using RNA sequencing analyses and a series of in vitro experiments, we confirm that the MAGL blockade-induced enhancement of BMSC osteogenic differentiation is primarily mediated by the phosphoinositide 3-kinases (PI3K)/ the serine/threonine kinase (AKT)/ (glycogen synthase kinase-3 beta) GSK3β pathway. Additionally, MAGL blockade can also reduce GC-induced bone resorption by directly suppressing osteoclastogenesis and indirectly reducing the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) in BMSCs. Thus, our study proposes that the therapeutic effect of MAGL blockade on ONFH is partly mediated by restoring the balance of bone homeostasis and MAGL may be an effective therapeutic target for ONFH.

01 Nov 2024·Biomedicine & Pharmacotherapy

Modulation of chemotherapy-induced peripheral neuropathy by JZL195 through glia and the endocannabinoid system

Article

Author: Nan, Guanghai ; Kim, Leejeong ; Cha, Myeounghoon ; Lee, Bae Hwan ; Kim, Hee Young

Chemotherapy-induced peripheral neuropathy (CIPN) used to treat cancer, is a significant side effect with a complex pathophysiology, and its mechanisms remain unclear. Recent research highlights neuroinflammation, which is modulated by the endocannabinoid system (ECS) and associated with glial activation, and the role of toll-like receptor 4 (TLR4) in CIPN. This study aimed to investigate the effects of JZL195, an inhibitor of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and explore the connection between cannabinoid receptors and TLR4 in glial cells. A CIPN animal model was developed using cisplatin-injected male C57BL/6 mice. Mechanical and cold allodynia were assessed through von Frey and acetone tests. Western blot analysis was used to examine the expression of catabolic enzymes, cannabinoid receptors, glial cells, and neuroinflammatory factors in the dorsal root ganglia (DRGs) and spinal cord. Immunohistochemistry was used to investigate the colocalization of cannabinoid receptors and TLR4 in glial cells. JZL195 alleviated pain by inhibiting FAAH/MAGL, modulating the ECS and neuroinflammatory factors, and suppressing glial cell activity. Additionally, cannabinoid receptors and TLR4 colocalized with astrocytes and microglia in the spinal cord. This study highlights the therapeutic potential of JZL195 in modulating the ECS and suggests a correlation between cannabinoid receptors and TLR4 in spinal glial cells, providing insight into alleviating pain and neuroinflammation in CIPN.

News (Medical) associated with MAGL

11 Apr 2023

·www.prnewswire.com

DelveInsight Evaluates a Robust Epilepsy Pipeline as 70+ Influential Pharma Players to Set Foot in the Domain

The prevalence of Epilepsy has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of Epilepsy and the growing research and development activities to develop novel therapies to treat Epilepsy to drive the market. The companies developing the potential therapies in the last stage of development include Xenon Pharmaceuticals, Engage Therapeutics, Janssen Biotech, and several others LAS VEGAS, April 11, 2023 /PRNewswire/ -- DelveInsight's ' Epilepsy Pipeline Insight – 2023 ' report provides comprehensive global coverage of available, marketed, and pipeline epilepsy therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the epilepsy pipeline domain. Key Takeaways from the Epilepsy Pipeline Report DelveInsight's epilepsy pipeline report depicts a robust space with 70+ active players working to develop 75+ pipeline therapies for epilepsy treatment. Key epilepsy companies such as Alexza Pharmaceuticals, Xenon Pharmaceuticals, GW Pharmaceuticals, Equilibre Biopharmaceuticals, Takeda Pharmaceuticals, Abide therapeutics, Otsuka pharmaceutical, H. Lundbeck A/S, Spark Therapeutics, Equilibre Biopharmaceuticals, ES Therapeutics, Supernus Pharmaceuticals, Inc., MGC Pharmaceuticals, Engrail Therapeutics INC, SK biopharmaceuticals, Longboard Pharmaceuticals, Janssen Research & Development, LLC, Equilibre Biopharmaceuticals, Cerevel Therapeutics, LLC, Neurona Therapeutics, Praxis Precision Medicines, UCB Pharma, Receptor Life Sciences, NeuroPro Therapeutics, Inc., Avicanna, Amring Pharmaceuticals Inc., Ovid Therapeutics, Addex Therapeutics, IAMA Therapeutics, CODA Biotherapeutics, Cerebral Therapeutics, Engrail Therapeutics, and others are evaluating new epilepsy drugs to improve the treatment landscape. Promising epilepsy pipeline therapies in various stages of development include Alprazolam, XEN1101, XEN-496, XEN 901, GWP42006, EQU-001, TAK-935, Lu AG06466, OPC-214870, CG 01, EQU-001, ES-481, SPN-817, MGCND00EP1, NBI 827104, ENX-101, Cenobamate, SKL-24741, LP-352, JNJ-40411813, EQU-001, CVL-865, NRTX 1001, PRAX 628, Padsevonil, RLS103, NPT 2042, AVCN-319302, PRAX-020, AMZ002, OV 350, IAMA-6, CT-010, ENX-101, and others. In March 2023, IAMA Therapeutics, a preclinical-stage pharmaceutical company focused on the discovery, development, and commercialization of novel medicines to make a difference in the lives of individuals suffering from brain disorders, announced that preclinical data supporting its IAMA-6 program in focal refractory epilepsy will be presented at the 75th American Academy of Neurology (AAN) Annual Meeting, taking place on April 22-27 in Boston, Massachusetts. In February 2023, Addex Therapeutics announced that enrollment into Part 1 of Phase 2 clinical study of ADX71149 (JNJ-40411813) for the treatment of epilepsy had been completed. ADX71149 is a selective metabotropic glutamate type 2 (mGlu2) receptor-positive allosteric modulator (PAM). Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, is conducting the trial. In January 2023, Equilibre Biopharmaceuticals Corp., reported positive topline results from the Phase 2 clinical trial evaluating the clinical safety, tolerability, and preliminary efficacy of EQU-001 – a novel anti-inflammatory anti-seizure medication - administered as once-daily oral adjunctive therapy for focal seizures in adults with epilepsy. The results of the EQU-001 study are encouraging because they demonstrate impressive tolerability and encouraging efficacy for adult patients with focal epilepsy, especially for those with seizures that are difficult to treat. In January 2023, Signant Health, introduced a novel electronic diary (eDiary) data capture solution designed to simplify the experience for patients and research sites participating in epilepsy trials while ensuring robust outcome assessment data to support trial endpoints. Developed in collaboration with The Epilepsy Study Consortium (TESC), the new patient-reported outcome measure offers clinical research sponsors and organizations a standardized solution to capture common seizure data elements with high-quality data. In June 2022, CODA Biotherapeutics, Inc. announced that preclinical data from the Company's focal epilepsy program demonstrated that treatment with the Company's lead-engineered receptor and small molecule activator drug significantly reduced focal seizure frequency in vivo. Results showed that the rapid reduction in seizures is consistent with the pharmacokinetics of the activator drug in mouse models. Data also demonstrated that the expression of CODA's lead receptor is highly correlated with a reduction in seizure frequency. In September 2022, Avicanna Inc. was pleased to announce that it has expanded its research collaboration in the field of Epilepsy with a new collaboration with the University of Toronto and Dr. Mac Burnham's research team to explore the efficacy of Avicanna's proprietary formulations in pre-clinical models for Epilepsy. The research collaboration led by Dr. Mac Burnham's team will explore the efficacy of Avicanna's drug candidates, including AVCN319302, in animal models for Epilepsy. In December 2022, Praxis Precision Medicines, Inc. and UCB announced a strategic collaboration, based upon Praxis' PRAX-020 program, for the discovery of small molecule therapeutics as potential treatments of KCNT1-related epilepsies. Under the terms of the collaboration, UCB retains an exclusive option to in-license global development and commercialization rights to any resulting KCNT1 small molecule development candidate. In January 2022, Ovid Therapeutics Inc. announced the company has entered into an exclusive license agreement with AstraZeneca for a library of early-stage small molecules targeting the KCC2 transporter, including lead candidate OV350. The company seeks to optimize and accelerate the development of these KCC2 transporter activators in epilepsies and potentially other neuropathic conditions. In August 2021, Marinus Pharmaceuticals, Inc. announced that it has entered into an agreement with Orion Corporation whereby Orion received exclusive rights to commercialize the oral and intravenous (IV) dose formulations of ganaxolone in the European Economic Area, United Kingdom, and Switzerland for CDKL5 deficiency disorder (CDD), tuberous sclerosis complex (TSC) and refractory status epilepticus (RSE). Request a sample and discover the recent advances in epilepsy drug treatment @ Epilepsy Pipeline Report The epilepsy pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage epilepsy drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the epilepsy clinical trial landscape. Epilepsy Overview Epilepsy is a chronic condition characterized by unprovoked, recurrent seizures. A seizure is an uncontrollable surge of electrical activity in the brain. Seizures are classified into two types. Seizures that affect the entire brain are known as generalized seizures. Focal seizures, also known as partial seizures, affect only one part of the brain. A mild seizure can be difficult to detect. It can last a few seconds, and you are unaware of it. Stronger seizures, lasting from a few seconds to several minutes, can cause spasms and uncontrollable muscle twitches. Epilepsy symptoms vary according to the area of the brain where seizure activity occurs and the type of seizure. Epilepsy symptoms may include: stiff muscles, Become stiff and falling backward, muscles relaxing and going floppy, confusion, breathing becomes difficult, unconscious, visual disturbances/hallucinations, uncontrollable jerking and shaking, called a "fit," losing awareness and staring blankly into space, strange sensations, such as a "rising" feeling in the tummy, unusual smells or tastes, and a tingling feeling in your arms or legs and collapsing. Epilepsy treatment can help most people with epilepsy have fewer seizures or completely stop having seizures. Find out more about drugs for epilepsy @ New Epilepsy Drugs A snapshot of the Epilepsy Pipeline Drugs mentioned in the report: Learn more about the emerging epilepsy pipeline therapies @ Epilepsy Clinical Trials Epilepsy Therapeutics Assessment The epilepsy pipeline report proffers an integral view of epilepsy emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Epilepsy Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-articular, Intraocular, Intrathecal, Intravenous, Ophthalmic, Oral, Parenteral, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: KCNQ potassium channel agonists, Monoacylglycerol lipase inhibitors, Cholesterol 24-hydroxylase inhibitors, NMDA receptor modulators, AMPA receptor antagonists, GABA A receptor agonists, Cannabinoid receptor modulators Key Epilepsy Companies: Alexza Pharmaceuticals, Xenon Pharmaceuticals, GW Pharmaceuticals, Equilibre Biopharmaceuticals, Takeda Pharmaceuticals, Abide therapeutics, Otsuka pharmaceutical, H. Lundbeck A/S, Spark Therapeutics, Equilibre Biopharmaceuticals, ES Therapeutics, Supernus Pharmaceuticals, Inc., MGC Pharmaceuticals, Engrail Therapeutics INC, SK biopharmaceuticals, Longboard Pharmaceuticals, Janssen Research & Development, LLC, Equilibre Biopharmaceuticals, Cerevel Therapeutics, LLC, Neurona Therapeutics, Praxis Precision Medicines, UCB Pharma, Receptor Life Sciences, NeuroPro Therapeutics, Inc., Avicanna, Amring Pharmaceuticals Inc., Ovid Therapeutics, Addex Therapeutics, IAMA Therapeutics, CODA Biotherapeutics, Cerebral Therapeutics, Engrail Therapeutics, and others. Key Epilepsy Pipeline Therapies: Alprazolam, XEN1101, XEN-496, XEN 901, GWP42006, EQU-001, TAK-935, Lu AG06466, OPC-214870, CG 01, EQU-001, ES-481, SPN-817, MGCND00EP1, NBI 827104, ENX-101, Cenobamate, SKL-24741, LP-352, JNJ-40411813, EQU-001, CVL-865, NRTX 1001, PRAX 628, Padsevonil, RLS103, NPT 2042, AVCN-319302, PRAX-020, AMZ002, OV 350, IAMA-6,CT-010, ENX-101, and others. Dive deep into rich insights for new drugs for epilepsy treatment; visit @ Epilepsy Medications Table of Contents For further information on the epilepsy pipeline therapeutics, reach out @ Epilepsy Drug Treatment Related Reports Epilepsy Market Epilepsy Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key epilepsy companies including Takeda Pharmaceuticals, Abide therapeutics, Otsuka pharmaceutical, among others. Epilepsy Epidemiology Forecast Epilepsy Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epilepsy epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Refractory Epilepsy Pipeline Refractory Epilepsy Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key refractory epilepsy companies, including Eisai Co.LTD., Alexza Pharmaceuticals, Xenon Pharmaceuticals, among others. Partial Epilepsy Pipeline Partial Epilepsy Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key partial epilepsy companies, including GW Pharmaceuticals, Equilibre Biopharmaceuticals, among others. Refractory Epilepsy Market Refractory Epilepsy Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key refractory epilepsy companies including Eisai Co.LTD., Alexza Pharmaceuticals, Xenon Pharmaceuticals, among others. Partial Epilepsy Market Partial Epilepsy Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key partial epilepsy companies, including GW Pharmaceuticals, Equilibre Biopharmaceuticals, among others. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

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