Drug Development Research最新文献

{"title":"Novel Benzimidazole-Pyridine-Phenylalkanesulfonate Hybrids: Design, Synthesis, Antimicrobial Screening, Lanosterol 14α-Demethylase Inhibition Properties and in Silico Studies","authors":"Aisha A. K. Al-Ashmawy,&nbsp;Mohamed Abdelraof,&nbsp;Asmaa Saleh,&nbsp;Aladdin M. Srour","doi":"10.1002/ddr.70122","DOIUrl":"https://doi.org/10.1002/ddr.70122","url":null,"abstract":"<div>\u0000 \u0000 <p>A newly designed benzimidazole-pyridine-pheylalkanesulfonate hybrids (<b>3a-r</b>) were synthesized through the regioselective Michael addition reaction between 2-acetyl-1-substituted-benzimidazole (<b>1</b>) and dicyano vinyl alkanesulfonate (<b>2</b>) to evaluate their activity against diverse microbial pathogens including <i>Candida albicans</i> (a unicellular fungus), <i>Bacillus subtilis</i> and <i>Staphylococcus aureus</i> (Gram-positive bacteria), as well as <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, and <i>Salmonella typhimurium</i> (Gram-negative bacteria). Although most of the tested hybrids showed promising antimicrobial potentiality, the MIC was calculated for the two precursors <b>1a</b>,<b>b</b> in addition to derivatives <b>3b</b>, <b>3 g</b>, <b>3k</b>, <b>3 m</b> and <b>3p</b> that found to prevent the proliferation of all microbial pathogens with different ratios in comparison to the reference drug used. Compound <b>3k</b> demonstrated the best anti-candida properties with MIC = 5 <i>μ</i>g/mL (amphotericin B, MIC = 20 <i>μ</i>g/mL), and it was of equal efficacy to ciprofloxacin against <i>Staphylococcus aureus</i> with MIC = 20 <i>μ</i>g/mL. Derivatives <b>3b</b> and <b>3 m</b> displayed equipotent activity to ciprofloxacin with MICs = 10 <i>μ</i>g/mL against <i>S. typhimurium</i> and <i>B. subtilis</i>, respectively. Moreover, derivative <b>3 m</b> exhibited 42.1% biofilm inhibition against <i>P. aeruginosa</i> (compared with 39.8% for Ciprofloxacin). An acceptable safety profile of the most potent derivatives was detected. The impact of the <b>3b</b> and <b>3k</b> hybrids on the tested microbial pathogens was visualized using CLSM. Furthermore, <b>3k</b> inhibited the Lanosterol 14α-demethylase (CYP51) with IC₅₀ = 4.2 <i>μ</i>M (fluconazole IC₅₀ = 0.6 <i>μ</i>M). Furthermore, in silico studies including ADME prediction for the five promising hits and molecular docking simulation of <b>3k</b> in the demethylase binding site were performed.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Biological Evaluation of Potent FLT3 Inhibitor for Acute Myeloid Leukemia (AML) Treatment","authors":"Kun Du,&nbsp;Yanan he,&nbsp;Jinyang Fu,&nbsp;Guimin Xue,&nbsp;Zhiqiang Zhang,&nbsp;Xiaokun Li,&nbsp;Yanle Zhi","doi":"10.1002/ddr.70119","DOIUrl":"https://doi.org/10.1002/ddr.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is a clonal malignant proliferative disease of myeloid progenitor cells in the hematopoietic system, with a lower than 5-year overall survival rate. At present, three FLT3 inhibitors have been approved, but these drugs are prone to cause resistance after a period of medication. Developing new FLT3 inhibitors with novel structures is an effective strategy to enhance drug treatment efficacy. This study presents an extension of our effort to design and synthesize a series of novel pyrimidine-2,4-diamine derivatives as inhibitors of FLT3. The most active compound, <b>7r</b>, showed significant inhibition against FLT3 with IC₅₀ value of 7.82 nM. In addition, <b>7r</b> exhibited prominent anticancer activities against AML cell lines, such as MV4-11 (IC₅₀ = 46.07 nM) and MOLM-13 (IC₅₀ = 51.6 nM). Compound <b>7r</b> inhibited phosphorylation of FLT3 pathways in a dose-dependent manner in MV4-11 cell lines.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Organoid-Based Drug Discovery: Revolutionizing Precision Medicine and Pharmacology","authors":"Dilpreet Singh,&nbsp;Akshay Thakur,&nbsp; Rakesh,&nbsp;Akshay kumar","doi":"10.1002/ddr.70121","DOIUrl":"https://doi.org/10.1002/ddr.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>Organoids, 3D cellular models derived from stem cells, have revolutionized drug testing by providing human-relevant systems for modeling diseases and testing drug efficacy. Unlike traditional 2D cell cultures or animal models, organoids closely resemble the complex architecture and function of human tissues, offering more accurate predictions of drug responses. Researchers are increasingly utilizing these models in oncology, neurology, liver toxicity, and personalized medicine. Recent advances in gene editing (e.g., CRISPR-Cas9), multi-omics technologies, and organoid-on-chip systems have further enhanced the capabilities of organoids in drug discovery. CRISPR-Cas9 allows for precise modeling of genetic disorders, while multi-omics approaches integrate transcriptomics, proteomics, and metabolomics to provide deeper insights into drug metabolism and toxicity. Organoid-on-chip platforms combine organoid culture with microfluidic systems, enabling the simulation of organ interactions and real-time drug testing. AI and machine learning models now enhance these platforms by predicting drug responses and optimizing high-throughput screening. Despite these advancements, challenges such as scalability, reproducibility, and the incomplete recapitulation of complex organ functions remain. Organoids hold the promise of significantly reducing reliance on animal models, improving the accuracy of drug testing, and paving the way for personalized treatments. This review outlines the latest innovations in organoid-based drug discovery, highlighting their potential to transform modern pharmacology and precision medicine, while acknowledging the ongoing efforts to address existing limitations.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Glucuronidase Inhibition in Drug Development: Emerging Strategies for Mitigating Drug-Induced Toxicity and Enhancing Therapeutic Outcomes","authors":"Ahmed A. Allam,&nbsp;Hassan A. Rudayni,&nbsp;Noha A. Ahmed,&nbsp;Faris F. Aba Alkhayl,&nbsp;Al Mokhtar Lamsabhi,&nbsp;Emadeldin M. Kamel","doi":"10.1002/ddr.70118","DOIUrl":"https://doi.org/10.1002/ddr.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>β-glucuronidase (βG) is a critical enzyme involved in the hydrolysis of glucuronide conjugates, significantly influencing drug metabolism, detoxification processes, and enterohepatic circulation. Although essential for maintaining physiological homeostasis, dysregulated βG activity has been implicated in diverse pathological conditions, including drug-induced toxicity, inflammation, and hormone-dependent cancers. Specifically, microbial βG expressed by gut microbiota can reactivate glucuronide-conjugated drugs, leading to adverse reactions through increased drug toxicity and reduced therapeutic efficacy. Consequently, inhibition of βG has emerged as an attractive therapeutic approach to reduce chemotherapy-induced toxicity, gastrointestinal complications, and metabolic disorders. This review systematically examines recent progress in the discovery, characterization, and optimization of βG inhibitors, focusing on natural products, synthetic molecules, and microbiome-targeted agents. Structure–activity relationship analyses reveal crucial functional groups and chemical modifications necessary for enhancing inhibitor potency, selectivity, and bioavailability. In addition, contemporary advances in βG inhibitor evaluation through enzyme kinetics, molecular docking simulations, high-throughput screening, and preclinical animal models are discussed, alongside essential pharmacokinetic parameters, including absorption, distribution, metabolism, excretion, and potential drug-drug interactions. Furthermore, emerging approaches such as microbiome modulation, CRISPR-based enzyme engineering, and combination therapies are explored. Despite promising preclinical outcomes, significant challenges remain regarding clinical translation, such as selectivity, bioavailability, and regulatory compliance. Ultimately, this review highlights future opportunities in precision medicine, emphasizing personalized βG inhibitor development to optimize therapeutic safety and effectiveness across various disease states.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring 2-Thioxo-1,2,3,4-tetrahydropyrimidines as Dual Acting GSK-3β/Aβ Aggregation Inhibitors: Implications for Alzheimer's Disease Treatment","authors":"Sukanya Sukanya,&nbsp;Aina Bellver-Sanchis,&nbsp;Bhanwar Singh Choudhary,&nbsp;Sunil Kumar,&nbsp;Belén Pérez,&nbsp;Antón Leandro Martínez Rodríguez,&nbsp;Jose Brea,&nbsp;Carmen Escolano,&nbsp;Christian Griñán-Ferré,&nbsp;Ruchi Malik","doi":"10.1002/ddr.70112","DOIUrl":"https://doi.org/10.1002/ddr.70112","url":null,"abstract":"<div>\u0000 \u0000 <p>The etiology of Alzheimer's disease (AD) is complex and multifactorial. There is a pressing need for therapies that can prevent or slow AD progression. Consequently, drug development has shifted from single-target approaches to multi-faceted strategies that emphasize early intervention rather than late-stage treatment. One promising target is glycogen synthase kinase-3β (GSK-3β), an enzyme implicated in tau hyperphosphorylation and Aβ plaque formation. Based on our earlier work, we synthesized 25 2-thioxo-1,2,3,4-tetrahydropyrimidine derivatives designed as GSK-3β inhibitors, tau phosphorylation inhibitors, and Aβ accumulation. Two compounds emerged as particularly effective: compound 63 (IC₅₀ = 1.69 µM) and compound 66 (IC₅₀ = 0.90 µM), with compound 66 identified as an ATP-competitive inhibitor of GSK-3β. Further pharmacokinetic studies and in vitro drug metabolism assessments were conducted, followed by in vivo efficacy studies using <i>Caenorhabditis elegans</i>. Notably, these compounds reduced phosphorylated tau levels in the BR5706 strain and decreased Aβ aggregate deposition in the CL2006 strain. Molecular Dynamic (MD) simulations were also performed on both compounds. These findings provide valuable insights into GSK-3β drug development and highlight the potential of these inhibitors as therapeutic candidates for AD by targeting both tau and Aβ, the two pathological hallmarks of AD.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Investigation of Tyrosinase Inhibitors: Past, Present, and Future","authors":"Yuanyuan Wang,&nbsp;Ruijia Jiang,&nbsp;Baichen Xiong,&nbsp;Jiawei Zhu,&nbsp;Jingjing Sang,&nbsp;Hongtao Li,&nbsp;Chen Chen,&nbsp;Ziwei Xu,&nbsp;Weiting Zhang,&nbsp;Yao Chen,&nbsp;Feng Feng,&nbsp;Haopeng Sun","doi":"10.1002/ddr.70113","DOIUrl":"https://doi.org/10.1002/ddr.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Tyrosinase (EC 1.14.18.1) is a pivotal enzyme that catalyzes the conversion of L-tyrosine to dopaquinone through a dual oxidation process, initiating melanin biosynthesis. Melanin plays a critical role in various biological processes, and its overproduction is associated with multiple conditions. Tyrosinase plays a crucial role in immune regulation by regulating the activity of immune cells and enhancing the immune response of the body. It is essential for maintaining skin health and preventing autoimmune diseases. In addition, tyrosinase has shown potential in immunotherapy, especially in the treatment of malignant melanoma and autoimmune diseases such as vitiligo. Inhibiting tyrosinase to reduce melanin synthesis has emerged as a promising therapeutic strategy with applications in skin whitening, melasma treatment, acne management, Parkinson's disease (PD) intervention, melanoma prevention, and overcoming immunotherapy resistance. By leveraging the tyrosinase-related comprehensive data documented in the BRENDA database, we have systematically summarized the effective information, including its classification, structural characteristics, catalytic functions, biosynthesis pathways, substrate specificity profiles, reaction products, and associated disease mechanisms, and so forth. This review comprehensively examines the therapeutic mechanisms, development history, and current clinical status of tyrosinase inhibitors at preclinical and advanced stages. We highlight recent research progress, focusing on evidence from animal models, preclinical studies, and human clinical trials across different indications. Additionally, we critically analyze the challenges and limitations in the field and provide insights into future directions for optimizing tyrosinase inhibitors. By synthesizing current knowledge and advancements, this review aims to underscore the therapeutic potential of tyrosinase inhibition and its role in addressing diverse medical needs.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferitrin Regulates the Proliferation, Metastasis, and Immune Escape of Nonsmall Cell Lung Cancer by Inhibiting the Akt/NF-κB Pathway","authors":"Zhenliang Shi,&nbsp;Yimeng Shen,&nbsp;Xin Liu,&nbsp;Sipei Zhang","doi":"10.1002/ddr.70117","DOIUrl":"https://doi.org/10.1002/ddr.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>Nonsmall cell lung cancer (NSCLC) is the most popular type of lung cancer with high morbidity. Kaempferitrin possesses the antitumor effect, while its role in NSCLC development and metastasis remains elusive. Thus, this study aimed to clarify the influence of Kaempferitrin on NSCLC development and elucidate the possible mechanism. In this study, cell viability, apoptosis, invasion, and angiogenesis were assessed using CCK-8, flow cytometry, Transwell invasion, and tube formation assays, respectively. The NF-κB nuclear translocation was observed via Immunofluorescence. In vivo, tumor growth was monitored in a xenograft model, with HE and TUNEL staining assessing tissue damage and apoptosis. Results revealed that Kaempferirin decreased NSCLC cell viability, induced cell apoptosis and suppressed cell motility dose-dependently. Additionally, Kaempferirin restrained the immune escape of NSCLC cells and inactivated the AKT/NF-κB pathway. SC79 could counteract the above effects of Kaempferirin on A549 cells. Moreover, Kaempferirin restrained tumor growth, metastasis and immune escape of NSCLC In vivo. In summary, Kaempferirin inhibited cell proliferation, invasion, angiogenesis, and immune escape and promoted apoptosis of NSCLC by inactivating the AKT/NF-κB pathway. Kaempferirin may be a hopeful drug for NSCLC therapy.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Metronidazole Conjugates as Antimicrobial Agents","authors":"Erol Akgün,&nbsp;Melike Demirayak,&nbsp;Leyla Yurttaş,&nbsp;Ülkiye Dudu Gül,&nbsp;Şeref Demirayak","doi":"10.1002/ddr.70114","DOIUrl":"https://doi.org/10.1002/ddr.70114","url":null,"abstract":"<p>Metronidazole (MTZ) is one of the oldest and still used anti-infective nitroimidazole group drug. Although it is effective against anaerobic bacteria, protozoa, and parasites in clinical settings, it lacks efficacy against aerobic microorganisms. Due to its efficient molecular structure and synthetic usability due to the alcohol group in its framework, medicinal chemists aimed to reach new more effective molecules such as MTZ-hybrids. In this study, 2-[(benzimidazole/benzoxazole/benzothiazol-2-yl)thio]-<i>N</i>-[2-(2-methyl-5-nitro-1<i>H</i>-imidazol-1-yl)ethyl]acetamide (<b>5a−5j</b>) derivatives were synthesized and their antimicrobial and antifungal effects on aerobic bacteria and <i>Candida</i> spp. were investigated. Notably, most of newly designed conjugates displayed higher potency than MTZ itself, especially against Gram-positive strains. Furthermore, chlorinated heterocyclic moieties provided the strongest effects. Docking studies using <i>E. coli</i> nitroreductase (PDB: 1IDT) revealed potential interactions with the flavin mononucleotide (FMN) cofactor, suggesting that these hybrids may undergo nitro-group reduction analogous to MTZ. Additionally, pharmacokinetic predictions indicated generally favorable profiles.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxindole–Coumarin Hybrids With Broad-Spectrum Anticancer Activity: Apoptosis Induction and Selective CA IX/XII Targeting","authors":"Hend I. Abdelaal,&nbsp;Abdalla R. Mohamed,&nbsp;Mohamed R. Elnagar,&nbsp;Simone Giovannuzzi,&nbsp;Samar H. Fahim,&nbsp;Hatem A. Abdel-Aziz,&nbsp;Claudiu T. Supuran,&nbsp;Sahar M. Abou-Seri","doi":"10.1002/ddr.70116","DOIUrl":"https://doi.org/10.1002/ddr.70116","url":null,"abstract":"<div>\u0000 \u0000 <p>A scaffold hybridization approach was utilized to enhance the antitumor and carbonic anhydrase inhibitory activity of our oxindole and coumarin lead compounds (<b>V</b> and <b>X</b>). Two oxindole-coumarin hybrids <b>6c</b> and <b>6e</b> showed broad spectrum of anticancer activity with NCI full panel MG-MIDs of 5.01 and 6.31 µM, respectively. They revealed GI₅₀ of a single digit micromolar concentration against 46 and 39 cell lines, respectively. An apoptosis dependent mechanism is suggested for the potent anticancer activity of compounds <b>6c</b> and <b>6e</b> via the increase in the BAX/BCL-2 ratio and enhancement of the expression levels of caspase-9 and the tumor suppressor p53. While this structure hybridization resulted in enhanced antitumor activity, it resulted in moderate CA IX and XII inhibitory activity. The potent anticancer compound <b>6e</b> was among the most active inhibitors of the tumor associated CA IX and CA XII in this study (K_I = 1.8 and 2.1 μM, respectively). As a result, even compound <b>6e</b>'s moderate CA IX/XII inhibitory activity may have synergistic effects contributing to its increased tumor growth suppression and proapoptotic activity. Moreover, compound <b>6e</b> revealed a nonsignificant cytotoxicity toward the normal kidney epithelial Vero cell line and was totally inactive against the cytosolic isoforms CA I and CA II (K_I = &gt; 100 μM) which mitigate its side effect as chemotherapeutic agent and enforce its safety profile.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding of the Role of TREM2 in Neuropathic Pain: Molecular Pathway and Neuroinflammatory Mechanism","authors":"Nithya Vijayan,&nbsp;Punniyakoti Veeraveedu Thanikachalam,&nbsp;Saraswati Patel","doi":"10.1002/ddr.70111","DOIUrl":"https://doi.org/10.1002/ddr.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuropathic pain is a debilitating condition characterized by chronic pain that is often refractory to conventional treatments. Increasing evidence suggests that microglia, the resident immune cells of the central nervous system, play a crucial role in modulating pain pathways through neuroinflammatory mechanisms. The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), in conjunction with DNAX-activating protein 12 (DAP12), regulates microglial activation and immune responses, thereby influencing neuropathic pain progression. This review explores the molecular mechanisms by which TREM2 contributes to pain modulation, focusing on its role in microglial activation, cytokine release, oxidative stress, and neuronal sensitization. Furthermore, we discuss the therapeutic potential of targeting TREM2 signaling for neuropathic pain management. Understanding the interplay between TREM2 and neuroinflammation offer novel insights into developing targeted interventions for chronic pain conditions.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}