Synthesis of Arginase Inhibitors: An Overview

Pharmaceutics, Год журнала: 2025, Номер 17(1), С. 117 - 117

Опубликована: Янв. 16, 2025

Arginase (ARG) is a binuclear manganese-containing metalloenzyme that can convert L-arginine to L-ornithine and urea plays key role in the cycle. It also mediates different cellular functions processes such as proliferation, senescence, apoptosis, autophagy, inflammatory responses various cell types. In mammals, there are two isoenzymes, ARG-1 ARG-2; they functionally similar, but their coding genes, tissue distribution, subcellular localization, molecular regulation distinct. recent decades, abnormal expression of or ARG-2 has been reported be increasingly linked variety diseases, including cardiovascular disease, bowel Alzheimer's cancer. Therefore, considering current relevance this topic need address growing demand for new more potent ARG inhibitors context review was conceived. We will provide an overview all classes developed so far compounds synthetic, natural, semisynthetic origin. For first time, synthesis protocol optimized reaction conditions each molecule, those patent applications, described. its inhibitory activity terms IC50 towards specifying type assay conducted.

Язык: Английский

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Optimization of citrulline production from a Bacillus subtilis BH-01 isolated from raw buffalo milk

BMC Microbiology, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 10, 2025

Abstract The main purpose of this study was to optimize the L-citrulline production process using Plackett-Burman and Box-Behnken designs. L-citrulline-producing bacterium BH-01 isolated from raw buffalo milk. isolate tested for probiotic activities such as tolerance simulated gastric intestinal juices, antagonistic activity against six antibiotic-resistant bacteria, temperature tolerance. arginine deiminase (ADI) were optimized statistical bacterial molecularly identified Bacillus subtilis strain AUMC B-498 (accession number PP574248.1). exhibited resistance at pH 2.0 bile salt 0.5% a two-hour exposure period. It could inhibit growth Escherichia coli , Klebsiella pneumonia Serratia sp., Staphylococcus aureus methicillin - resistant (MRSA), Streptococcus pneumoniae. From results optimization, design temperature, L-arginine, incubation period, peptone most effective factors among eight selected variables. Based on these, used required maximize citrulline production. maximum 632.5 µg/L, ADI 1.42 U/mL. Therefore, Buffalo milk might be promising candidate in food, biotechnological, pharmaceutical applications due its dual functionality characteristics.

Язык: Английский

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Differential Expression of ARG1 and MRC2 in Retinal Müller Glial Cells During Autoimmune Uveitis

Biomolecules, Год журнала: 2025, Номер 15(2), С. 288 - 288

Опубликована: Фев. 14, 2025

Retinal Müller glial cells (RMG) play a crucial role in retinal neuroinflammation, including autoimmune uveitis. Increasing evidence supports their function as active modulators of immune responses and potential atypical antigen-presenting (APCs). To further investigate this hypothesis, we conducted differential proteome analysis primary equine RMG from healthy controls horses with recurrent uveitis (ERU), spontaneous model This identified 310 proteins abundance. Among these, the Major Histocompatibility Complex (MHC) class II enzyme Arginase 1 (ARG1) were significantly enriched uveitis-affected horses, whereas Mannose Receptor C-type 2 (MRC2) its interactor Thrombospondin (THBS1) more abundant RMG. The detection MHC RMG, consistent previous studies, validates robustness our approach. Furthermore, identification ARG1 MRC2, together THBS1, provides new insights into immunomodulatory properties Immunohistochemical analyses confirmed proteomic findings revealed spatial distribution MRC2. MRC2 are thus markers for neuroinflammatory or physiological milieu highlight differences particularly antigen presentation.

Язык: Английский

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Not All Neuroinflammation Is Created Equal: The Dual Nature of Astrogliosis

Biological Psychiatry, Год журнала: 2025, Номер 97(8), С. 758 - 760

Опубликована: Март 27, 2025

Язык: Английский

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Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity

Опубликована: Апрель 1, 2025

Metabolic reprogramming within the tumor microenvironment (TME) plays a central role in cancer progression and immune evasion, with L-arginine metabolism emerging as key regulatory axis. Arginase overexpression depletes intratumoral L-arginine, thus suppressing T-cell proliferation while fuelling growth through polyamine biosynthesis. OATD-02, novel dual arginase (ARG1/ARG2) inhibitor, reprograms by restoring availability reducing levels of polyamines, thereby shifting TME toward more immunostimulatory state. Unlike ARG1-selective inhibitors limited intracellular uptake, OATD-02 effectively inhibits both extracellular arginases, addressing major limitation first-generation inhibitors. To visualize pharmacodynamic effects dosing mice spatial resolution, we employed MALDI mass spectrometry imaging (MALDI-MSI), enabling direct mapping metabolic changes tissues. In preclinical models, treatment led to widespread accumulation concomitant depletion polyamines resulted shifts that correlated increased cell infiltration an improved response checkpoint blockade. These findings underscore inhibition reshaping overcoming suppression fitness cells fight cancer. The caused significantly enhanced antitumor responses, tumors, expansion CD8⁺ T draining lymph nodes, systemic upregulation activation markers. translated into substantial survival benefit CT26 model, particularly when combined anti-PD-1 therapy, where blockade efficacy relieving constraints affecting tumor-infiltrating lymphocytes. By leveraging unique capabilities MALDI-MSI, this study provides high-resolution insights mechanism action reinforcing its potential next-generation metabolic-immunotherapeutic agent. observed reprogramming, coupled prolonged survival, supports clinical development promising strategy for enhancing immunotherapy efficacy. is currently undergoing evaluation phase I/II trial (NCT05759923), which will further elucidate safety therapeutic impact. highlight arginase-targeted therapies value MALDI-MSI powerful tool tracking responses therapy.

Язык: Английский

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DIA-based quantitative proteomic insight of lamb meat quality: tenderness and amino acid profile under different grazing intensities

LWT, Год журнала: 2024, Номер unknown, С. 117285 - 117285

Опубликована: Дек. 1, 2024

Язык: Английский

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