Chemical Biology & Drug Design最新文献

{"title":"Discovery of 1-(Cyclopropylmethyl)-2-(Dibenzo[b,d]Thiophen-2-yl)-1H-Benzo[d]Imidazole-5-Carboxylic Acid as Orally Bioavailable EP4 Receptor Antagonist","authors":"Sanjay Kumar,&nbsp;Rajib Chakraborty,&nbsp;Chandreyee Roy,&nbsp;Sohini Basu,&nbsp;Arun K. Hajra,&nbsp;Priyam Sen,&nbsp;Debajyoti Paul,&nbsp;Karabi Phukan,&nbsp;Subhasis Roy,&nbsp;Rammohan Bera,&nbsp;Trisha Mondal,&nbsp;Sabyasachi Chakraborty,&nbsp;Manish Banerjee,&nbsp;Susanta K. Mondal,&nbsp;Sonali Das,&nbsp;Pradip Malik,&nbsp;Surajit De Mandal,&nbsp;Enketeswara Subudhi,&nbsp;Mrinalkanti Kundu","doi":"10.1111/cbdd.70132","DOIUrl":"https://doi.org/10.1111/cbdd.70132","url":null,"abstract":"<div>\u0000 \u0000 <p>The prostaglandin E₂ (PGE₂) regulates several biological processes via interaction with 1 of 4 E-type prostanoid receptors (EP1–EP4). The E-type prostanoid receptor 4 (EP4) is expressed primarily on myeloid cells, T lymphocytes, and tumor cells, and has emerged as a major contributor to PGE₂-mediated enhancement of tumor survival pathways and as a suppressor of innate and adaptive antitumor immune responses. To date, significant work on the discovery of EP4 receptor antagonists has been carried out, but no compound has been approved for use in humans yet. Toward our aim of discovering potential EP4 antagonists, a pharmacophore-based scaffold-hopping approach combined with docking studies has been envisaged. As a result, compound 4 was found to be a non-toxic, potent EP4 antagonist binding in the orthosteric site. This compound exhibited good aqueous solubility, with acceptable in vitro metabolic stability and permeability. Albeit high protein binding, it displayed sustained exposure and significant oral bioavailability in mice and can thus have the potential for further optimization to yield next-generation EP4 antagonists.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179190","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 Activity of 8-Hydroxyurolithin A Class PDE2 Inhibitors","authors":"Qiulin Hu,&nbsp;Long Tang,&nbsp;Zhongqiu Xu,&nbsp;Fen Yan,&nbsp;Guoqiang Song,&nbsp;Xiaoqing Feng","doi":"10.1111/cbdd.70119","DOIUrl":"https://doi.org/10.1111/cbdd.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Urolithin A (UA) is a dibenzo[<i>b,d</i>]pyran-6-one polyhydroxy derivative produced as intestinal microbe metabolize ellagitannin and ellagic acid. Because of its superior anti-inflammatory and antioxidant effects, it can cure neuronal damage in a variety of ways and play a neuroprotective role. More and more research has revealed that UA is a potential medicine for the treatment of neurodegenerative diseases. Due to UA source limitations, it is insufficient to achieve disease treatment concentrations, and the activity of UA inhibiting PDE2 needs further enhancement. As a result, we used UA as the parent nucleus structure, independently designed and used Discovery Studio software to assist in the structural design and molecular docking screening of the compounds, and tested the in vitro enzyme activity of the synthesized compounds, hoping to obtain UA-based PDE2 inhibitors. The IC₅₀ of 6–18, 6–19, 6–20, 6–22, and 6–29 were 0.62, 0.85, 1.51, 1.09, and 1.58 μM, respectively. In this study, UA derivatives that can bind to the crystal structure of PDE2 protein 4HTX were proposed, which laid a groundwork for further structural modification, lead design, and development of small molecule inhibitors with inhibitory activity of PDE2.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148354","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":"Synthesis of Novel Thiazole/Thiadiazole Conjugates of Fluoroquinolones as Potent Antibacterial and Antimycobacterial Agents","authors":"Pınar Poyraz Yılmaz,&nbsp;Necla Kulabaş,&nbsp;Arif Bozdeveci,&nbsp;Siva Krishna Vagolu,&nbsp;Mohd Imran,&nbsp;Esra Tatar,&nbsp;Şengül Alpay Karaoğlu,&nbsp;Dharmarajan Sriram,&nbsp;Ammar A. Razzak Mahmood,&nbsp;İlkay Küçükgüzel","doi":"10.1111/cbdd.70126","DOIUrl":"https://doi.org/10.1111/cbdd.70126","url":null,"abstract":"<p>Twenty azole-fluoroquinolone hybrids were designed and synthesized by conjugating thiazole and thiadiazole structures to ciprofloxacin and norfloxacin via a 2-oxoethyl bridge. The structures and purities of the synthesized compounds were proven by spectral techniques. The antimycobacterial effects of target compounds <b>21–40</b> were tested against <i>Mycobacterium tuberculosis</i> H37Rv strain. Among the 20 synthesized compounds, 12 exhibited minimal inhibition concentration (MIC) values in the range of 1.56–25 μg/mL. Among the molecules screened for antimycobacterial effects, the most effective was compound <b>35</b>, a thiadiazole-ciprofloxacin hybrid. The cytotoxic effect of this molecule was found to be lower than the reference drugs, and it was also determined to be a more effective inhibitor than ciprofloxacin and norfloxacin in the DNA-gyrase supercoiling test. The antimicrobial effects of compounds <b>21–40</b> were screened by agar-well diffusion and microdilution tests against Gram-positive/negative bacteria, a fast-growing mycobacterium, and two yeast strains. While most of the compounds tested showed antibacterial effects, the most effective fluoroquinolone derivative appeared to be compound <b>31</b> with an MIC value of &lt; 0.63 μg/mL against all Gram-negative bacteria tested. Azole-fluoroquinolone hybrids <b>21–40</b> did not show any activity against non-pathogenic <i>Lactobacillus</i> species and yeast-like fungi, indicating that they have selective antibacterial and antimycobacterial activity, particularly against Gram-negative bacteria. <i>In silico</i> molecular docking studies were conducted to uncover the interactions between lead compound <b>35</b> and the DNA gyrase proteins of <i>M. tuberculosis</i> and <i>S. aureus</i>. Additionally, a 100 ns molecular dynamics simulation was carried out to assess the stability of the complexes formed between compound <b>35</b> and both proteins.</p>","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":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135680","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":"Design, Synthesis and Biological Evaluation of POLRMT Inhibitors for the Treatment of Acute Myeloid Leukemia","authors":"Tianli Liu,&nbsp;Xiaoling Cheng,&nbsp;Yupeng Wang,&nbsp;Wenli Hao,&nbsp;Hangyu Wang,&nbsp;Ke Zhang,&nbsp;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}

{"title":"Design and Synthesized 3,4-Dimethoxybenzene-Based Fibrate Derivatives as Potential Hypolipidemic and Liver Protection Agents","authors":"Ling Ding,&nbsp;Yuyu An,&nbsp;Xinyi Shi,&nbsp;Huizi Shangguan,&nbsp;Xin Wang,&nbsp;Jiping Liu,&nbsp;Yongheng Shi,&nbsp;Xinya Xu,&nbsp;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}

{"title":"Structural Insights Into Papain-Derived Synthetic Antibacterial Peptides for Targeting Klebsiella pneumoniae","authors":"Marcos Antônio Ferreira,&nbsp;Patrícia Souza e Silva,&nbsp;Adriel Parahyba Lacerda,&nbsp;Pedro de Mattos Franco,&nbsp;Fhillipe Ferreira Deodato da Silva,&nbsp;Thalis Ferreira de Souza,&nbsp;Maria Ligia R. Macedo,&nbsp;Ludovico Migliolo,&nbsp;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}

{"title":"Discovery of Novel Inhibitors for WD Repeat-Containing Protein 5 (WDR5)-MYC Protein–Protein Interaction","authors":"Wei Sun,&nbsp;Huaxing Yu,&nbsp;Jiuyong Ye,&nbsp;Luoheng Qin,&nbsp;Linli Wang,&nbsp;Hailu Yan,&nbsp;Zhimin Zhang,&nbsp;Alex Aliper,&nbsp;Feng Ren,&nbsp;Xiao Ding,&nbsp;Alex Zhavoronkov,&nbsp;Dongzhou Liu","doi":"10.1111/cbdd.70129","DOIUrl":"https://doi.org/10.1111/cbdd.70129","url":null,"abstract":"<div>\u0000 \u0000 <p>The WD Repeat-Containing Protein 5 (WDR5) and MYC interaction is crucial for MYC-mediated oncogenesis, yet effective therapeutic intervention remains challenging due to the limited efficacy of current treatments targeting WDR5. Herein, we report the discovery of novel WDR5-MYC protein–protein interaction (PPI) inhibitors with improved potency and drug-like properties by utilizing a generative chemistry platform along with a physics-model-based tool AlChemistry. Initially, three hits were identified with reasonable binding affinity for WDR5, and further refinement through detailed structural analysis led to the discovery of sub-micromolar affinity compounds (compound <b>9c-1</b>), which are &gt; 30-fold better than reported inhibitors. These findings provide a promising starting point for targeting the WDR5-MYC interaction in MYC-driven cancers.</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":"144100740","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 Phenoxyacetic Acid (4-Aminophenoacetic Acid) Shikonin Ester Kills KRAS Mutant Colon Cancer Cells via Targeting the Akt Allosteric Site","authors":"Yudi Ma,&nbsp;Yuqian Sun,&nbsp;Qingqing Tu,&nbsp;Faxiang Lin,&nbsp;Feng Mei,&nbsp;Qingqing Chen,&nbsp;Ting Fu,&nbsp;Liu Yang,&nbsp;Xiaohui Lai,&nbsp;Minkai Yang,&nbsp;Tongming Yin,&nbsp;Guihua Lu,&nbsp;Jinliang Qi,&nbsp;Hongyan Lin,&nbsp;Zhongling Wen,&nbsp;Yonghua Yang,&nbsp;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 × 10⁻⁶ 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^G13D) and HCT-8 (KRAS^G12A) 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}

{"title":"Exploring Thiazole-Based Heterocycles: Synthesis, Bioactivity, and Molecular Docking for Antimicrobial Applications","authors":"Hana M. Abumelha,&nbsp;Fatmah O. Sefrji,&nbsp;Abdulmajeed F. Alrefaei,&nbsp;Mariam Mojally,&nbsp;Fatimah A. Alotaibi,&nbsp;Khadra B. Alomari,&nbsp;Fatimah M. Madkhaly,&nbsp;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}

{"title":"Current Challenges With Highly Active Antiretroviral Therapy and New Hope and Horizon With CRISPR-CAS9 Technology for HIV Treatment","authors":"Akmal Zubair,&nbsp;Arooba Sujan,&nbsp;Muhammad Ali,&nbsp;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}