Review
Chemistry, Medicinal
Shivani Jaiswal, Senthil Raja Ayyannan
Summary: Recently, FAAH and MAGL inhibitors have attracted attention for their potential anticancer effects. By regulating endogenous ligands, these inhibitors show therapeutic effects in chronic pain, metabolic disorders, psychoses, among others, and exhibit potential in various types of cancers.
Article
Pharmacology & Pharmacy
William G. Warren, Eleni P. Papagianni, Ed Hale, Rebecca A. Brociek, Helen J. Cassaday, Carl W. Stevenson
Summary: Endocannabinoid transmission plays an important role in treating anxiety-related disorders through the regulation of fear extinction. The inhibition of FAAH can enhance extinction by increasing anandamide levels, while inhibiting MAGL can impair extinction by elevating 2-arachidonoylglycerol levels. However, the specific effects of endocannabinoids on fear relapse and extinction resistance are still uncertain.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Neurosciences
Shivanshu Bajaj, Shreshta Jain, Preeti Vyas, Sandhya Bawa, Divya Vohora
Summary: Alzheimer's disease is a neurodegenerative disease with potential therapeutic targets in the endocannabinoid system. Inhibitors of monoacylglycerol (MAGL) and fatty acid amide hydrolase (FAAH) possess multi-faceted properties for the treatment of Alzheimer's disease.
BRAIN RESEARCH BULLETIN
(2021)
Article
Biochemistry & Molecular Biology
Ziad Omran
Summary: Novel disulfiram derivatives were evaluated as potent inhibitors of MAGL, showing high selectivity over FAAH. Compound 2i displayed low micromolar inhibition of MAGL without inhibitory activity against FAAH.
Article
Chemistry, Medicinal
Shivani Jaiswal, Senthil Raja Ayyannan
Summary: By utilizing a ligand-based design strategy, a series of isatin-3-carbohydrazones were synthesized and evaluated for their dual FAAH and MAGL inhibition properties. The study identified potent inhibitors, with compounds 13b and 13j being the most effective against MAGL and FAAH respectively, while compound 13c exhibited dual inhibitory activity and significant antioxidant properties in cell-based assays. These compounds showed promising pharmacokinetic profiles for treating neurological and mood disorders.
Article
Immunology
Murat Cakir, Ali Aydin, Suat Tekin
Summary: This study investigated the effects of MAGL inhibitor KML29 and FAAH inhibitor URB597 on kidney ischemia-reperfusion injury. The results showed that administration of KML29 and URB597 can reduce kidney damage and inflammation caused by IR. The study suggests that inhibition of MAGL and FAAH may be a new therapeutic strategy for preventing kidney IR injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Shivani Jaiswal, Garima Gupta, Senthil R. Ayyannan
Summary: This study designed and synthesized a series of carbamate compounds and evaluated their dual FAAH-MAGL inhibition properties. Compound 2e, 3h, and 2i showed the strongest inhibitory effects. Enzyme kinetics experiments revealed that these compounds inhibit FAAH/MAGL in a mixed binding mode of covalent-reversible manner. Additionally, docking simulation experiments and ADMETox prediction studies provided useful information for further investigation.
ARCHIV DER PHARMAZIE
(2022)
Review
Pharmacology & Pharmacy
Ming Tatt Lee, Ken Mackie, Lih-Chu Chiou
Summary: This review explores the potential and contributions of activating the endocannabinoid system and peripheral neuromodulation in opioid tolerance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Neurosciences
Jocelyne Alcaraz-Silva, Daniel Feingold, Gerardo Viana-Torre, Henning Budde, Claudio Imperatori, Sergio Machado, Eric Murillo-Rodriguez
Summary: This study reviews the evidence on the role of the endocannabinoid system in the diagnosis and treatment of depression and anxiety. The results suggest that the endocannabinoid system could be a potential strategy for mood disorders, but further research is needed.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Article
Biochemistry & Molecular Biology
Shivani Jaiswal, Akhilesh, Ankit Uniyal, Vinod Tiwari, Senthil Raja Ayyannan
Summary: Researchers have discovered a promising lead compound for the treatment of neuropathic pain by designing and synthesizing a series of compounds. The lead compound exhibited potent inhibition activity against both FAAH and MAGL, and showed good safety profile in vivo experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chaoling Chen, Weili Wang, Justin L. Poklis, Aron H. Lichtman, Joseph K. Ritter, Gaizun Hu, Dengpiao Xie, Ningjun Li
Summary: The study suggests that FAAH activation and the consequent reduction of AEA contribute to renal fibrogenesis, while FAAH inhibition protects against fibrogenesis in renal cells independently of CB receptors via the AEA-COX-2 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Review
Cell Biology
Alessandro Papa, Silvia Pasquini, Chiara Contri, Sandra Gemma, Giuseppe Campiani, Stefania Butini, Katia Varani, Fabrizio Vincenzi
Summary: Polypharmacology challenges the traditional paradigm of one-drug, one target, one disease by using multitarget compounds for the treatment of complex diseases. The endocannabinoid system is an attractive therapeutic target in central nervous system disorders and neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Tiziana Genovese, Andrea Duranti, Ramona D'Amico, Roberta Fusco, Daniela Impellizzeri, Alessio Filippo Peritore, Rosalia Crupi, Enrico Gugliandolo, Salvatore Cuzzocrea, Rosanna Di Paola, Rosalba Siracusa, Marika Cordaro
Summary: Acute lung injury (ALI) is a lung disease characterized by severe inflammation without treatment. This study investigated the role of fatty acid amide hydrolase (FAAH) inhibition in an ALI mouse model and found that it could counteract the inflammatory response and histological changes caused by the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Roberta Ottria, Silvana Casati, Paola Rota, Pierangela Ciuffreda
Summary: A simple and efficient synthesis of an endogenous agonist for cannabinoid receptors, 2-AG, was achieved using a two-step enzymatic process and chemical coupling. The method offers a high yield and negligible presence of isomerization product, and does not require extensive purification steps.
Article
Hematology
Sarah Rieck, Sofia Kilgus, Johanna H. Meyer, Hao Huang, Lan Zhao, Michaela Matthey, Xin Wang, Steffen Schmitz-Valckenberg, Bernd K. Fleischmann, Daniela Wenzel
Summary: The study demonstrates that inactivation of FAAH impairs angiogenesis by increasing endogenous anandamide levels, which represents a novel antiangiogenic mechanism. This finding highlights the importance of exploring new pharmacological targets for antiangiogenic therapy in diseases characterized by pathological angiogenesis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)