ArticleEBioMedicine2019
Paradoxical effects of JZL184, an inhibitor of monoacylglycerol lipase, on bone remodelling in healthy and cancer-bearing mice.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Classical cannabinoid receptors as target in cancer-induced bone pain: a systematic review, meta-analysis and bioinformatics validation.Scientific reports · 2024Pooled it
- The biological functions of monoacylglycerol lipase (MAGL) in cancer.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Protective Effects of Monoacylglycerol Lipase Inhibition in Rats with Severe Acute Pancreatitis and Its Possible MechanismEndocrine, metabolic & immune disorders drug targets · 2026Article
- CRLS1 influences liver metastasis in colon cancer by regulating lipid metabolism pathways.Functional & integrative genomics · 2025Article
- Deciphering the role of monoacylglycerol lipases (MAGL) under abiotic stress and lipid metabolism in soybean (Glycine max L.).Plant biotechnology journal · 2025Article
- Metabolism, a Blossoming Target for Small-Molecule Anticancer Drugs.Molecules (Basel, Switzerland) · 2025Review
- Integrative multi-omics investigation of sleep apnea: gut microbiome metabolomics, proteomics and phenome-wide association study.Nutrition & metabolism · 2025Article
- Article
- Mechanisms of Abnormal Lipid Metabolism in the Pathogenesis of Disease.International journal of molecular sciences · 2024Review
- The role of the sensory input intervention in recovery of the motor function in hypoxic ischemic encephalopathy rat model.Journal of neurophysiology · 2024Article
- Article
- Article
- The Metabolic Landscape of Breast Cancer and Its Therapeutic Implications.Molecular diagnosis & therapy · 2023Review
- Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic strategy for neurodegenerative diseases.Pharmacology & therapeutics · 2023Review
- Animal models of cancer metastasis to the bone.Frontiers in oncology · 2023Review
- Endocannabinoid Metabolism and Transport as Drug Targets.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis.Signal transduction and targeted therapy · 2022Article
- Cannabinoids as anticancer drugs: current status of preclinical research.British journal of cancer · 2022Review
- Inhibition of triple negative breast cancer-associated inflammation, tumor growth and brain colonization by targeting monoacylglycerol lipase.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer-associated bone disease is a serious complication in bone sarcomas and metastatic carcinomas of breast and prostate origin. Monoacylglycerol lipase (MAGL) is an enzyme of the endocannabinoid system, and is responsible for the degradation of the most abundant endocannabinoid in bone, 2-arachidonoyl glycerol (2AG).
methodsThe effects of the verified MAGL inhibitor on bone remodelling were assessed in healthy mice and in mouse models of bone disease caused by prostate and breast cancers and osteosarcoma.
findingsJZL184 reduced osteolytic bone metastasis in mouse models of breast and prostate cancers, and inhibited skeletal tumour growth, metastasis and the formation of ectopic bone in models of osteosarcoma. Additionally, JZL184 suppressed cachexia and prolonged survival in mice injected with metastatic osteosarcoma and osteotropic cancer cells. Functional and histological analysis revealed that the osteoprotective action of JZL184 in cancer models is predominately due to inhibition of tumour growth and metastasis. In the absence of cancer, however, exposure to JZL184 exerts a paradoxical reduction of bone volume via an effect that is mediated by both Cnr1 and Cnr2 cannabinoid receptors.
interpretationMAGL inhibitors such as JZL184, or its novel analogues, may be of value in the treatment of bone disease caused by primary bone cancer and bone metastasis, however, activation of the skeletal endocannabinoid system may limit their usefulness as osteoprotective agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.