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.
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
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)
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
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
Sanela Rajlic, Luise Surmann, Pia Zimmermann, Christina Katharina Weisheit, Laura Bindila, Hendrik Treede, Markus Velten, Andreas Daiber, Georg Daniel Duerr
Summary: Ischemic cardiomyopathy leads to inflammation and left ventricular dysfunction. Animal studies suggest that the endocannabinoid system may have cardioprotective effects, including cardiomyocyte adaptation, inflammation, and remodeling. This study investigates the potential cardioprotective effect of the endocannabinoid anandamide (AEA) after ischemia and reperfusion using FAAH (-/-) mice and suggests that increased endocannabinoids may have detrimental effects on cardiomyocyte survival due to PPAR-alpha activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Veterinary Sciences
Vikram Thakur, Mohammad Bashashati, Josue Enriquez, Munmun Chattopadhyay
Summary: This study assessed specific gastrointestinal symptoms in Type 1 diabetic mice and evaluated treatment options for this condition. The results showed that inhibiting endocannabinoid degradation may have a therapeutic effect on gastrointestinal dysmotility.
VETERINARY SCIENCES
(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
Chemistry, Medicinal
Giulia Bononi, Giulio Poli, Flavio Rizzolio, Tiziano Tuccinardi, Marco Macchia, Filippo Minutolo, Carlotta Granchi
Summary: This review discusses patents related to new MAGL inhibitors and their potential therapeutic applications published since 2018. In the years 2018-2020, several known chemical scaffolds of MAGL inhibitors have been further optimized and developed, along with the identification of new chemical classes as MAGL inhibitors. The focus on MAGL-specific PET ligands in scientific publications and efforts from pharmaceutical companies and academic groups demonstrate the rapid growth in this research area.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Keisuke Takahata, Chie Seki, Yasuyuki Kimura, Manabu Kubota, Masanori Ichise, Yasunori Sano, Yasuharu Yamamoto, Kenji Tagai, Hitoshi Shimada, Soichiro Kitamura, Kiwamu Matsuoka, Hironobu Endo, Hitoshi Shinotoh, Kazunori Kawamura, Ming-Rong Zhang, Yuhei Takado, Makoto Higuchi
Summary: This study demonstrates the first visualization of MAGL in the human brain using the novel PET ligand F-18-T-401. The results confirm the reliability of F-18-T-401-PET for quantification and stability analysis of MAGL in vivo.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
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)
Article
Chemistry, Medicinal
Maximilian Barth, Stefan Rudolph, Jan Kampschulze, Imke Meyer zu Vilsendorf, Walburga Hanekamp, Dennis Mulac, Klaus Langer, Matthias Lehr
Summary: A series of hexafluoroisopropyl carbamates with indolylalkyl- and azaindolylalkyl-substituents were synthesized and tested for inhibition of the endocannabinoid degrading enzymes FAAH and MAGL. The compounds with alkyl chains incorporated into a piperidine ring showed selective MAGL inhibition, while an extension of the alkyl spacer resulted in dual FAAH/MAGL inhibition. The reactive hexafluoroisopropyl carbamate group was found to be mainly responsible for the inhibitory effect. Some derivatives showed slightly higher MAGL inhibition and improved physicochemical and biochemical properties compared to the known MAGL inhibitor ABX-1431.
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)
Article
Biochemistry & Molecular Biology
Soojung Hahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Summary: This study utilized three-dimensional intestinal organoids to investigate the effects of metformin on inflammatory bowel disease (IBD) and found that metformin can enhance intestinal barrier function and reduce levels of inflammatory cytokines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
V. V. Sudarev, M. S. Gette, S. V. Bazhenov, O. M. Tilinova, E. V. Zinovev, I. V. Manukhov, A. I. Kuklin, Yu. L. Ryzhykau, A. V. Vlasov
Summary: This study investigated the self-assembly processes of ferritin-based protein complexes and obtained structurally characterized oligomeric states. These results provide new potential and opportunities for the application of ferritin in various fields.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Yalda Sabaghi, Farnaz Pourfarzad, Leila Zolghadr, Azita Bahrami, Tahereh Shojazadeh, Alireza Farasat, Nematollah Gheibi
Summary: p-Coumaric acid (p-CA) is a plant compound with anti-cancer activities. This study designed a nano-liposomal carrier containing p-CA to enhance its effectiveness against melanoma cells. The findings showed that the liposomal form of p-CA had a greater impact on the cells. Kinetic modeling indicated that the best fitting model was zero-order.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
M. D. Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura
Summary: This study investigated the expression of ncRNAs other than miRNAs in different histologic subtypes of canine mammary gland tumors (MGT). Three aberrantly expressed ncRNAs were identified as potential biomarkers for differentiating MGT subtypes. YRNA and tRFs expression levels were found to be decreased in metastatic compared to primary MGT cell lines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Seine A. Shintani
Summary: In this study, the researchers used signal analysis to study the instantaneous amplitude and phase of sarcomeric oscillations in skeletal muscle. They identified two types of oscillations, sarcomeric oscillations and sarcosynced oscillations, and visualized their behavior during propagating waves. The researchers discovered the presence of sarcomeric defect holes and sarcomeric collision holes, which are important indicators for understanding the oscillation properties of sarcomeres. This finding has important implications for improving our understanding of muscle function and its regulatory mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuanglin Zhang, Yuzhong Jia, Guolan Ma, Yanyan Yang, Zhenzhen Cao, Antao Luo, Zefu Zhang, Shihan Li, Jie Wen, Hanfeng Liu, Jihua Ma
Summary: Bupleurum is an antiarrhythmic agent that may exert its effects by inhibiting L-type calcium channels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Tomotaka Ohkubo, Yasuhiko Matsumoto, Hiroaki Sasaki, Kaoru Kinoshita, Yuki Ogasawara, Takashi Sugita
Summary: This study found that Citrobacter koseri inhibits the growth of Staphylococcus epidermidis, disrupting the balance between S. epidermidis and Staphylococcus aureus, and exacerbating inflammation in atopic dermatitis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Toshifumi Asano, Philipp Sasse, Takao Nakata
Summary: A Cre recombination-based fluorescent reporter system was developed to monitor cell-cell fusion. The system successfully detected the formation of multinuclear myotubes and placental syncytiotrophoblast. This tool could facilitate the study of cell-to-cell fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Ke Shi, Yunlong Shan, Xiao Sun, Kuida Chen, Qiong Luo, Qiang Xu
Summary: This study found that low expression of TP53INP2 is associated with poor survival in colorectal cancer (CRC) patients. As the malignancy of CRC progresses, TP53INP2 expression gradually decreases. Knockdown of TP53INP2 promotes CRC cell proliferation and tumor growth. Mechanistically, TP53INP2 deficiency decreases phosphorylation of beta-catenin, leading to increased accumulation and enhanced nuclear translocation and transcriptional activity. Additionally, TP53INP2 sequesters TIM50, inhibiting its activation of beta-catenin. In conclusion, downregulation of TP53INP2 promotes CRC progression by activating beta-catenin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Martina Rossi, Fabio Tomaselli, Alejandro Hochkoeppler
Summary: Oligomeric enzymes are known for their higher catalytic rates compared to monomeric enzymes, but the extent of additivity in their activity is still not well understood. This study used tetrameric rabbit lactate dehydrogenase as a model to examine the kinetics of its catalytic action. Surprisingly, when the concentration of the limiting reactant exceeded that of a single subunit, there was a significant slowdown in the enzyme's conformational rearrangements.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Amin Sahraei, Mohammad Javad Shamsoddini, Fakhrossadat Mohammadi, Leila Hassani
Summary: This study explored the inhibitory effects of gallium curcumin, indium curcumin, and vanadyl curcumin on the amyloid fibrillation of hen egg white lysozyme, as well as the binding interactions of these metal complexes with the enzyme. The results showed that indium curcumin and vanadyl curcumin exhibited higher binding affinities and stronger inhibitory effects on amyloid fibrillation compared to gallium curcumin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa
Summary: PGRN deficiency plays a significant role in cardiac remodeling and arrhythmias post-myocardial infarction (MI), potentially by promoting metabolic abnormalities in macrophages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Hongwei Zhao, Yiqiang Li, Yibo Zhang, Chi Zhang
Summary: Electrical brain stimulation technology is commonly used to treat brain neurological disorders, but it can cause side effects. This study investigated the impact of electric fields on nerve fibers and revealed the possible origin of side effects. The findings provide guidance for selecting electrical parameters in clinical stimulation therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Julia S. Scott, Lake-Ee Quek, Andrew J. Hoy, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler
Summary: The fatty acid elongation enzyme ELOVL5 plays a critical role in promoting metastasis in prostate cancer. Knocking down ELOVL5 leads to the accumulation of malonyl-CoA, which inhibits fatty acid oxidation in mitochondria. This study highlights the importance of fatty acid elongation in regulating cell viability and provides a potential target for prostate cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Zan Zhou, Wen-jun Jiang, Li Li, Jun-qiang Si
Summary: This study investigates the effect of noise exposure on cognitive function in mice and explores the underlying molecular mechanisms. The findings suggest that noise exposure leads to increased inflammation, increased phosphorylation of Tau protein, and decreased levels of postsynaptic density protein, resulting in cognitive impairment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)