Chemical Biology & Drug Design最新文献_第7页

Design, Synthesis and Biological Evaluation of POLRMT Inhibitors for the Treatment of Acute Myeloid Leukemia 急性髓系白血病POLRMT抑制剂的设计、合成及生物学评价

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-25 DOI: 10.1111/cbdd.70127

Tianli Liu, Xiaoling Cheng, Yupeng Wang, Wenli Hao, Hangyu Wang, Ke Zhang, Jinhui Wang

{"title":"Design, Synthesis and Biological Evaluation of POLRMT Inhibitors for the Treatment of Acute Myeloid Leukemia","authors":"Tianli Liu, Xiaoling Cheng, Yupeng Wang, Wenli Hao, Hangyu Wang, Ke Zhang, Jinhui Wang","doi":"10.1111/cbdd.70127","DOIUrl":"https://doi.org/10.1111/cbdd.70127","url":null,"abstract":"<div>\u0000 \u0000 <p>The metabolic dependence of acute myeloid leukemia (AML) cells on mitochondrial oxidative phosphorylation (OXPHOS) has become a cutting-edge area in cancer energy metabolism research, playing a pivotal role in cell survival and drug resistance. Consequently, targeted inhibition of human mitochondrial RNA polymerase (POLRMT) to block mitochondrial gene expression emerges as a novel potential strategy for treating AML through OXPHOS modulation. In this study, based on the previously reported crystal structure of the POLRMT inhibitor IMT1B, we employed a scaffold hopping strategy to design and synthesize a series of derivatives featuring additional hydrophobic occupying groups. A new potent POLRMT inhibitor (<b>10a</b>) was discovered, which displayed potent antiproliferative activity and could disrupt mitochondrial function and induce apoptosis in MOLM-13 cells. Together, these results demonstrate that <b>10a</b> is a new POLRMT inhibitor, which may provide a candidate lead for AML treatment.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131609","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}

引用次数: 0

Design and Synthesized 3,4-Dimethoxybenzene-Based Fibrate Derivatives as Potential Hypolipidemic and Liver Protection Agents 3,4-二甲氧基苯基纤维酸酯衍生物的设计与合成

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-23 DOI: 10.1111/cbdd.70123

Ling Ding, Yuyu An, Xinyi Shi, Huizi Shangguan, Xin Wang, Jiping Liu, Yongheng Shi, Xinya Xu, Yundong Xie

{"title":"Design and Synthesized 3,4-Dimethoxybenzene-Based Fibrate Derivatives as Potential Hypolipidemic and Liver Protection Agents","authors":"Ling Ding, Yuyu An, Xinyi Shi, Huizi Shangguan, Xin Wang, Jiping Liu, Yongheng Shi, Xinya Xu, Yundong Xie","doi":"10.1111/cbdd.70123","DOIUrl":"https://doi.org/10.1111/cbdd.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of 3,4-dimethoxybenzene-based fibrate derivatives were designed and synthesized, which were screened for preliminary lipid-lowering activity in a Triton WR-1339-induced hyperlipidemic mouse model. T5 had the strongest triglyceride (TG) and total cholesterol (TC) lowering effect among these target compounds. In a dose-dependent study, the lowering effects of T5 on TG and TC were progressively enhanced with increasing doses administered. Further studies revealed that T5 had a hypolipidemic significant effect on high-fat diet (HFD)-induced hyperlipidemia mouse model, with substantial reductions in TG, TC, and low-density lipoprotein cholesterol (LDL-C) levels, and a significant reduction in aspartate transaminase (AST) and alanine aminotransferase (ALT) levels in the liver, which had a protective effect on the liver. The of liver pathology showed that T5 could effectively inhibit lipid accumulation as well as inflammatory infiltration in the liver, thus reducing the degree of liver tissue damage. The expression of peroxisome proliferator-activated receptor-α (PPAR-α), which regulates lipid metabolism, was significantly upregulated in liver tissues. Molecular docking assays also confirmed the high binding affinity between T5 and PPAR-α active sites. In addition, T5 exhibited significant anti-inflammatory and antioxidant effects. These findings suggest that T5 has multiple activities and may be a potential novel hypolipidemic drug with hypolipidemic and hepatoprotective effects.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117993","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}

引用次数: 0

Structural Insights Into Papain-Derived Synthetic Antibacterial Peptides for Targeting Klebsiella pneumoniae 针对肺炎克雷伯菌的木瓜蛋白合成抗菌肽的结构分析

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-23 DOI: 10.1111/cbdd.70130

Marcos Antônio Ferreira, Patrícia Souza e Silva, Adriel Parahyba Lacerda, Pedro de Mattos Franco, Fhillipe Ferreira Deodato da Silva, Thalis Ferreira de Souza, Maria Ligia R. Macedo, Ludovico Migliolo, Jefferson Soares de Oliveira

{"title":"Structural Insights Into Papain-Derived Synthetic Antibacterial Peptides for Targeting Klebsiella pneumoniae","authors":"Marcos Antônio Ferreira, Patrícia Souza e Silva, Adriel Parahyba Lacerda, Pedro de Mattos Franco, Fhillipe Ferreira Deodato da Silva, Thalis Ferreira de Souza, Maria Ligia R. Macedo, Ludovico Migliolo, Jefferson Soares de Oliveira","doi":"10.1111/cbdd.70130","DOIUrl":"https://doi.org/10.1111/cbdd.70130","url":null,"abstract":"<p>Bacterial resistance represents one of the greatest challenges in modern medicine, requiring innovative strategies. This study presents the rational design of two synthetic analogue peptides, WK-MAP1, and WG-MAP2, inspired by the structure of the enzyme papain (PDB 9PAP), emphasizing the novelty of using an enzyme as a model for developing new antimicrobials. Initially, in silico studies, including molecular modeling and docking experiments, revealed a high affinity of the peptides for mimetic bacterial membranes. Subsequently, in vitro assays confirmed their antimicrobial efficacy. WK-MAP1 demonstrated superior activity against carbapenem-resistant <i>Klebsiella pneumoniae</i> (KPC+), with a minimum inhibitory concentration (MIC) of 25 μM, whereas WG-MAP2 exhibited activity against both tested strains (KPC+ and ATCC), with MICs of 50 and 100 μM, respectively. Both peptides effectively inhibited biofilm formation and exhibited low cytotoxicity in murine cells. This research highlights the potential of WK-MAP1 and WG-MAP2 as promising candidates for novel antimicrobial therapies, offering an innovative approach to overcoming the limitations of conventional antibiotics.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117991","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}

引用次数: 0

Discovery of Novel Inhibitors for WD Repeat-Containing Protein 5 (WDR5)-MYC Protein–Protein Interaction WDR5 -MYC蛋白相互作用新抑制剂的发现

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-21 DOI: 10.1111/cbdd.70129

Wei Sun, Huaxing Yu, Jiuyong Ye, Luoheng Qin, Linli Wang, Hailu Yan, Zhimin Zhang, Alex Aliper, Feng Ren, Xiao Ding, Alex Zhavoronkov, Dongzhou Liu

引用次数: 0

Novel Phenoxyacetic Acid (4-Aminophenoacetic Acid) Shikonin Ester Kills KRAS Mutant Colon Cancer Cells via Targeting the Akt Allosteric Site 新型苯氧乙酸（4-氨基苯乙酸）紫草素酯通过靶向Akt变构位点杀死KRAS突变结肠癌细胞

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-21 DOI: 10.1111/cbdd.70125

Yudi Ma, Yuqian Sun, Qingqing Tu, Faxiang Lin, Feng Mei, Qingqing Chen, Ting Fu, Liu Yang, Xiaohui Lai, Minkai Yang, Tongming Yin, Guihua Lu, Jinliang Qi, Hongyan Lin, Zhongling Wen, Yonghua Yang, Hongwei Han

{"title":"Novel Phenoxyacetic Acid (4-Aminophenoacetic Acid) Shikonin Ester Kills KRAS Mutant Colon Cancer Cells via Targeting the Akt Allosteric Site","authors":"Yudi Ma, Yuqian Sun, Qingqing Tu, Faxiang Lin, Feng Mei, Qingqing Chen, Ting Fu, Liu Yang, Xiaohui Lai, Minkai Yang, Tongming Yin, Guihua Lu, Jinliang Qi, Hongyan Lin, Zhongling Wen, Yonghua Yang, Hongwei Han","doi":"10.1111/cbdd.70125","DOIUrl":"https://doi.org/10.1111/cbdd.70125","url":null,"abstract":"<div>\u0000 \u0000 <p>The PI3K-Akt axis is abnormally activated in KRAS-mutated colorectal cancer and is considered to be a potential therapeutic target. A novel series of phenoxyacetic acid (4-aminophenoacetic acid) shikonin esters was designed by computer-aided drug design (CADD) and synthesized as Akt allosteric inhibitors. Most compounds exhibited greater anti-proliferative activity compared to the positive control MK2206, while also demonstrating lower cytotoxicity against normal cells than shikonin. One of the promising candidates, L8, was selected for further biological evaluation. Docking studies indicated that L8 effectively bound to the allosteric site of Akt through hydrophobic and hydrogen interactions. Enzyme activity and kinetics assessments revealed that L8 bound to Akt with a Kd of 2.07 × 10<sup>−6</sup> M and inhibited its activity. Further intracellular assays, including western blotting, enzyme activity assay, flow cytometry, etc., verified that L8 mediated the death of two KRAS-mutant colon cancer cell lines HCT116 (KRAS<sup>G13D</sup>) and HCT-8 (KRAS<sup>G12A</sup>) cells by inactivating Akt, causing tumor cell apoptosis, cell cycle arrest, and interfering with tumor cell invasion and metabolism. A 3D-QSAR model was constructed to understand the relationship between the structure of the shikonin derivatives and their anti-proliferative activity. The in silico ADMET and toxicity prediction studies revealed a few undesired pharmacokinetic attributes of our compounds.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100739","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}

引用次数: 0

Exploring Thiazole-Based Heterocycles: Synthesis, Bioactivity, and Molecular Docking for Antimicrobial Applications 探索噻唑类杂环化合物：合成、生物活性和抗菌应用的分子对接

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-21 DOI: 10.1111/cbdd.70124

Hana M. Abumelha, Fatmah O. Sefrji, Abdulmajeed F. Alrefaei, Mariam Mojally, Fatimah A. Alotaibi, Khadra B. Alomari, Fatimah M. Madkhaly, Nashwa M. El-Metwaly

{"title":"Exploring Thiazole-Based Heterocycles: Synthesis, Bioactivity, and Molecular Docking for Antimicrobial Applications","authors":"Hana M. Abumelha, Fatmah O. Sefrji, Abdulmajeed F. Alrefaei, Mariam Mojally, Fatimah A. Alotaibi, Khadra B. Alomari, Fatimah M. Madkhaly, Nashwa M. El-Metwaly","doi":"10.1111/cbdd.70124","DOIUrl":"https://doi.org/10.1111/cbdd.70124","url":null,"abstract":"<div>\u0000 \u0000 <p>In response to the rising threat of antimicrobial resistance, a novel series of thiazole-based heterocyclic compounds incorporating benzimidazole, benzoxazole, and benzothiazole via the reaction of 2-chloro-N-(4-(6-methyl-2,4-dioxo-3,4-dihydro-2H-pyran-3-yl)thiazol-2-yl) acetamide <b>(3)</b> with some mercapto derivatives. Pyrazolo[1,5-<i>a</i>]pyrimidine motifs were synthesized via the reaction of aminopyrazole derivative <b>9</b> with some electrophilic reagents and systematically characterized. The antimicrobial potential of these molecules was assessed against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, and <i>Candida albicans</i>. Among the tested derivatives, compounds <b>6</b>, <b>20</b>, and <b>22</b> emerged as particularly effective, with minimum inhibitory concentrations (MICs) reaching as low as 3.125 μg/mL. Structure–activity relationship (SAR) analysis highlighted the role of electron-withdrawing groups in enhancing bioactivity. Molecular docking studies further supported the experimental findings, showing favorable interactions with bacterial DNA gyrase (PDB ID: 1KZN). Additionally, SwissADME profiling revealed that the compounds possess promising drug-like properties and oral bioavailability. These findings position the synthesized thiazole-containing scaffolds as promising candidates for future antimicrobial drug development.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100877","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}

引用次数: 0

Current Challenges With Highly Active Antiretroviral Therapy and New Hope and Horizon With CRISPR-CAS9 Technology for HIV Treatment 高活性抗逆转录病毒疗法面临的挑战与CRISPR-CAS9技术治疗HIV的新希望和新前景

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-12 DOI: 10.1111/cbdd.70121

Akmal Zubair, Arooba Sujan, Muhammad Ali, Syeda Maryam Hussain

{"title":"Current Challenges With Highly Active Antiretroviral Therapy and New Hope and Horizon With CRISPR-CAS9 Technology for HIV Treatment","authors":"Akmal Zubair, Arooba Sujan, Muhammad Ali, Syeda Maryam Hussain","doi":"10.1111/cbdd.70121","DOIUrl":"https://doi.org/10.1111/cbdd.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>Clustered regularly interspaced short palindromic repeats (CRISPR/Cas system) is now the predominant approach for genome editing. Compared to conventional genetic editing methods, CRISPR/Cas technology offers several advantages that were previously unavailable. Key benefits include the ability to simultaneously modify multiple locations, reduced costs, enhanced efficiency, and a more user-friendly design. By directing Cas-mediated DNA cleavage to specific genomic targets and utilizing intrinsic DNA repair processes, this system can produce site-specific gene modifications. This goal is achieved through an RNA-guided procedure. As the most effective gene editing method currently available, the CRISPR/Cas system has proven to be highly valuable in genomic research across a wide range of species since its discovery as a component of the adaptive immune system in bacteria. Its applicability extends to various organisms, making it increasingly prevalent in the medical field, where it shows great promise in investigating viral infections, cancer, and genetic disorders. Furthermore, it enhances our understanding of fundamental genetics. This article outlines the current antiretroviral therapy and its adverse effects but also CRISPR/Cas technology. This review article also discusses its mechanism of action and potential applications in the treatment of HIV/AIDS.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938850","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}

引用次数: 0

Synthesis Methods and Therapeutic Journey of Carprofen and Its Derivatives: A Review 卡洛芬及其衍生物的合成方法及治疗历程综述

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-10 DOI: 10.1111/cbdd.70122

Carmen Limban, Diana Camelia Nuță, Miron Teodor Caproiu, Denisa Elena Dumitrescu, Șerban Iancu Papacocea, Alexandra Teodora Bordei, Florea Dumitrașcu

{"title":"Synthesis Methods and Therapeutic Journey of Carprofen and Its Derivatives: A Review","authors":"Carmen Limban, Diana Camelia Nuță, Miron Teodor Caproiu, Denisa Elena Dumitrescu, Șerban Iancu Papacocea, Alexandra Teodora Bordei, Florea Dumitrașcu","doi":"10.1111/cbdd.70122","DOIUrl":"https://doi.org/10.1111/cbdd.70122","url":null,"abstract":"<p>Carprofen, a nonsteroidal anti-inflammatory drug (NSAID) derived from propanoic acid, is known for its analgesic and antipyretic properties. Although it has long been employed in veterinary medicine as an anti-inflammatory agent, its use in humans was discontinued shortly after its market launch due to costly raw materials, complex synthesis, and labor-intensive production processes—factors that made it less competitive compared with other NSAIDs. Despite this, the carprofen molecule remains a subject of significant scientific interest. Recent advancements in its synthesis have introduced simplified and more cost-effective methods, reigniting its potential for both novel applications and drug repurposing. Exciting new research is exploring carprofen's broader therapeutic possibilities, extending beyond its original anti-inflammatory role. Studies are investigating its efficacy in antimicrobial therapy—including antibiofilm, anticancer, antiviral, and anti-Alzheimer's applications—opening doors to a wealth of untapped possibilities. This review delves into these emerging areas, highlighting how carprofen's molecular structure and derivatives can be leveraged to expand its therapeutic reach. The literature review was conducted using four databases: Web of Science, ScienceDirect, Scopus, Embase, and Reaxys. The review focused on English-language original research and review articles, examining carprofen and its derivatives in terms of their synthesis methods as well as their use as small molecules in various therapeutic applications, both human and veterinary. With ongoing research pushing the boundaries of its potential, carprofen remains a promising candidate for innovation in drug development and treatment strategies.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930377","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}

引用次数: 0

Artesunate Enhances Sensitivity of Renal Cancer Cells to Sunitnib by Mediating Tripartite Motif Containing 24-Induced Ubiquitination of Paired Box 6 青蒿琥酯通过介导含有24诱导的配对框6泛素化的三方基序增强肾癌细胞对舒尼替尼的敏感性

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-10 DOI: 10.1111/cbdd.70116

Zelin Cui, Jianhua Wen, Guanglin Yang, Liwei Wei, Hao Chen, Qiyue Zhao, Shubo Yang, Jiayin Yu, Yichen Huang, Shuting Tan, Qizhou Mo, Min Qin, Jiwen Cheng

{"title":"Artesunate Enhances Sensitivity of Renal Cancer Cells to Sunitnib by Mediating Tripartite Motif Containing 24-Induced Ubiquitination of Paired Box 6","authors":"Zelin Cui, Jianhua Wen, Guanglin Yang, Liwei Wei, Hao Chen, Qiyue Zhao, Shubo Yang, Jiayin Yu, Yichen Huang, Shuting Tan, Qizhou Mo, Min Qin, Jiwen Cheng","doi":"10.1111/cbdd.70116","DOIUrl":"https://doi.org/10.1111/cbdd.70116","url":null,"abstract":"<div>\u0000 \u0000 <p>This research aims to elucidate the mechanistic role of artesunate (ART) in enhancing the sensitivity of renal cell carcinoma (RCC) to sunitinib. To establish sunitinib-resistant RCC cell lines (786-O R and Caki-1 R), cells were treated with different concentrations of sunitinib and ART. The viability of the cells was measured through the cell counting kit-8 (CCK-8) assay. Tripartite motif-containing 24 (TRIM24) and paired box 6 (PAX6) expression were suppressed with lentiviral vectors, quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) analysis. TRIM24-PAX6 interaction was examined through co-immunoprecipitation (Co-IP) and deubiquitination assays. Additional assays included colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, WB detection of phosphorylated histone H2AX (γ-H2AX) for DNA damage, epithelial-mesenchymal transition (EMT) marker analysis, sphere formation, and stemness marker assessments. In vivo drug resistance was tested using a mouse subcutaneous xenograft model. ART enhanced sunitinib sensitivity in resistant RCC cells, reducing colony formation, inducing apoptosis, elevating γ-H2AX, and upregulating TRIM24. ART enhances sunitinib sensitivity in RCC cells by upregulating TRIM24 expression, which facilitates the ubiquitination of PAX6. This process leads to the suppression of EMT and stem cell-like transitions in RCC cells.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930378","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}

引用次数: 0

A Comprehensive Review on the Advancements of Dual COX-2/5-LOX Inhibitors as Anti-Inflammatory Drugs 双COX-2/5-LOX抑制剂抗炎研究进展综述

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-05-10 DOI: 10.1111/cbdd.70114

Neetu Agrawal

{"title":"A Comprehensive Review on the Advancements of Dual COX-2/5-LOX Inhibitors as Anti-Inflammatory Drugs","authors":"Neetu Agrawal","doi":"10.1111/cbdd.70114","DOIUrl":"https://doi.org/10.1111/cbdd.70114","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic pain and inflammation are widespread clinical issues that significantly affect patients' quality of life and are often associated with serious conditions such as arthritis, cancer, and cardiovascular disease. Effective management of inflammation is therefore a major public health priority. Current anti-inflammatory treatments—including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics—offer symptomatic relief but are frequently limited by side effects such as gastrointestinal toxicity, immunosuppression, or cardiovascular risks. Moreover, most of these therapies target only a single pathway in the inflammatory cascade. Dual inhibitors of COX-2 and 5-LOX have emerged as a promising therapeutic class, as they simultaneously block two key enzymes involved in prostaglandin and leukotriene synthesis. This dual-action approach offers enhanced efficacy and may reduce adverse effects linked to selective or non-selective COX inhibition. This review discusses the underlying mechanisms of inflammation, evaluates current treatment options, and highlights the pharmacological advantages and development status of dual COX-2/5-LOX inhibitors as a next-generation strategy for inflammation management.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930379","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}

引用次数: 0