Drug Design, Development and Therapy最新文献

{"title":"Ginsenoside Reshapes Intestinal Microecology to Alleviate Microgravity Stress.","authors":"Yanli Wang, Tian Chen, Zhe Shi, Lijinchuan Dong, Mengting Li, Bo Peng, Qi Li, Ruile Pan, Shuiming Xiao, Qing Yang, Ning Jiang, Xinmin Liu, Qin Hu, Ying Chen","doi":"10.2147/DDDT.S486371","DOIUrl":"https://doi.org/10.2147/DDDT.S486371","url":null,"abstract":"<p><strong>Background: </strong>During medium- to long-duration spaceflights, real-time microgravity can increase the health risks of astronauts. In particular, the disruption of intestinal homeostasis is closely related to other health problems, and it is necessary to monitor related treatment strategies. Ginseng is a well-known Chinese herbal medicine often used to maintain health. Ginseng total saponins (GTSs), which are the bioactive components of ginseng, have been reported to regulate immune homeostasis, anti-inflammation, and anti-oxidation. This study focused on the regulation of GTSs in intestinal homeostasis imbalance caused by microgravity.</p><p><strong>Methods: </strong>A hindlimb suspension (HLS) rat model was established to evaluate the intestinal protective effects of GTSs. Differentially expressed genes (DEGs) were screened using RNA-Seq. RT-PCR was performed to further focus and verify these results. The gut microbiome composition was examined based on 16S rRNA gene amplicon sequencing, and the short-chain fatty acids produced were further analyzed.</p><p><strong>Results: </strong>We found that GTSs intervention effectively improved the intestinal injury caused by simulated weightlessness, including reducing the pathological damage, increasing the expression of tight junction proteins and reducing the levels of inflammatory factors. Moreover, GTSs treatment significantly restored the levels of intestinal immunity-related genes and remodeled the gut microbiota. In particular, GTSs significantly increased the abundance of short-chain fatty acid metabolism-related bacteria, thereby increasing the level of propionic acid, butyric acid, isobutyric acid.</p><p><strong>Conclusion: </strong>Our results revealed that GTSs improved intestinal microecological disorders and impaired immune function caused by the weightlessness simulation. The underlying mechanism may be related to the \"intestinal immune -microbiota-metabolic\" pathway. These findings provide a theoretical basis for the precise design and development of GTSs for space-health products.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1289-1303"},"PeriodicalIF":4.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bibliometric and Visual Analysis of Oliceridine Research (2013-2024).","authors":"Cheng Song, Xinxing Huang, Nianping Chen, Qiliang Song, Yuanli Qiu","doi":"10.2147/DDDT.S497186","DOIUrl":"https://doi.org/10.2147/DDDT.S497186","url":null,"abstract":"<p><strong>Purpose: </strong>To explore and analyze the current research progress, hotspots, and future trends in oliceridine research using bibliometric methods.</p><p><strong>Patients and methods: </strong>We searched the Web of Science (WOS) database utilizing the keywords TS = (\"oliceridine*\" OR \"TRV 130*\" OR \"TRV-130*\" OR \"olinvyk*\" OR \"TRV130*\" OR \"C22H31CIN2O2S*\") for relevant research literature on oliceridine from its inception to June 16, 2024. Bibliometric methods were applied, and analysis software such as VOSviewer and CiteSpace were used to visualize the publication timeline, authors, countries and regions, keywords, sources of literature, research hotspots, and co-cited documents related to oliceridine. Co-occurrence and aggregation analyses were conducted, and maps relevant to institutional cooperation were generated.</p><p><strong>Results: </strong>A total of 151 relevant articles were retrieved and included in the final analysis. Most articles were published between 2020 and 2021. The United States has the highest number of publications and citations in this field. Molecular structure development is a pivotal point in this field. Research hotspots were diverse, including acute pain, opioid receptors, β-arrestin, postoperative pain, therapeutic window, respiratory depression, clinical trials, and chronic pain.</p><p><strong>Conclusion: </strong>Oliceridine, a newly developed analgesic, has garnered global interest. The USA is a leading contributor to this field. Recent research has shifted from basic studies to clinical practice.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1305-1321"},"PeriodicalIF":4.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RET Inhibitor SPP86 Is a Potential Candidate for the Clinical Treatment of Cutaneous Melanoma [Letter].","authors":"Yingjian Tan, Rui Li","doi":"10.2147/DDDT.S523115","DOIUrl":"10.2147/DDDT.S523115","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1249-1250"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Technology Assessment: Evaluation of 8 CGRP-Targeted Therapy Drugs for the Treatment of Migraine.","authors":"Mengyi Li, Siyong Huang, Jiabao Li, Xiao Hu, Jisheng Chen","doi":"10.2147/DDDT.S499848","DOIUrl":"10.2147/DDDT.S499848","url":null,"abstract":"<p><strong>Purpose: </strong>In order to scientifically evaluate the clinical value of the comprehensive attributes of Calcitonin gene-related peptide (CGRP) inhibitor drugs, a comprehensive literature-based clinical evaluation of CGRP-targeted therapy drugs was conducted using the drug evaluation method modified by expert discussion in the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition).</p><p><strong>Methods: </strong>Based on evidence-based data and the relevant elements and weighting in the \"Selection Guidelines\" quantification record form for drug evaluation and selection in medical institutions, adjustments were made according to the characteristics of CGRP-targeted therapy drugs. We systematically evaluated erenumab, galcanezumab, fremanezumab, eptinezumab, rimegepant, ubrogepant, atogepant, zavegepant for safety, efficacy, economy, and pharmacological properties.</p><p><strong>Results: </strong>The final assessment result scores from highest to lowest were rimegepant (84.5 points), erenumab (75.78 points), galcanezumab (74.02 points), fremanezumab (73.93 points), atogepant (72.64 points), eptinezumab (71.69 points), ubrogepant (70.37 points), zavegepant (56.44 points).</p><p><strong>Conclusion: </strong>Rimegepant, erenumab, fremanezumab, atogepant, galcanezumab, eptinezumab, ubrogepant can be entered into the medication list of medical institutions as strongly recommended drugs.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1231-1247"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic Analysis, Antiproliferative, Anti-Migratory, and Anti-Invasive Potential of Amlodipine in Lung Cancer Cells.","authors":"Mohammad A Y Alqudah, Mahmoud M Yaseen, Karem H Alzoubi, Belal A Al-Husein, Sanaa K Bardaweel, Ahmad Y Abuhelwa, Ahlam M Semreen, Ruba A Zenati, Raafat El-Awady, Mohd Shara, Yasser Bustanji, Nelson C Soares, Eman Abu-Gharbieh, Wafaa S Ramadan, Mohammad H Semreen","doi":"10.2147/DDDT.S484561","DOIUrl":"10.2147/DDDT.S484561","url":null,"abstract":"<p><strong>Background and objective: </strong>Lung cancer stands as the leading cause of cancer-related fatalities worldwide. While chemotherapy remains a crucial treatment option for managing lung cancer in both early-stage and advanced cases, it is accompanied by significant drawbacks, including severe side effects and the development of chemoresistance. Overcoming chemoresistance represents a considerable challenge in lung cancer treatment. Amlodipine cytotoxicity was previously demonstrated and could make lung cancer cells more susceptible to chemotherapies. This research aims to examine the metabolomics changes that may occur due to amlodipine's anticancer effects on non-small cell lung cancer (NSCLC) cells.</p><p><strong>Methods: </strong>Amlodipine's effects on A549 and H1299 NSCLC were evaluated using a colorimetric MTT assay, a scratch wound-healing assay and Matrigel invasion chambers to measure cell viability, cell migration and cell invasion. Ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) was used for the untargeted metabolomics investigation.</p><p><strong>Results: </strong>Our study revealed that amlodipine significantly reduced proliferation of cancer cells in a dose-dependent fashion with IC₅₀ values of 23 and 25.66 µM in A549 and H1299 cells, respectively. Furthermore, amlodipine reduced the invasiveness and migration of cancer cells. Metabolomics analysis revealed distinct metabolites to be significantly dysregulated (Citramalic acid, L-Proline, dGMP, L-Glutamic acid, Niacinamide, and L-Acetylcarnitine) in amlodipine-treated cells.</p><p><strong>Conclusion: </strong>The present study illustrates the anticancer effects of amlodipine on lung cancer proliferation, migration, and invasion in vitro and enhance our understanding of how amlodipine exerts its anticancer potential by casting light on these mechanisms.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1215-1229"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical Research Landscape of Intracranial Nicardipine for Aneurysmal Subarachnoid Hemorrhage: Insights From Bibliometric Analysis.","authors":"Guangtang Chen, Yi Cao, Xiaolin Du, Junshuan Cui, Xi Zeng, Hua Yang, Zeguang Ren, Kaya Xu","doi":"10.2147/DDDT.S503226","DOIUrl":"10.2147/DDDT.S503226","url":null,"abstract":"<p><strong>Background: </strong>The 2023 American Heart Association/American Stroke Association guideline and Wessels et al's 2024 randomized controlled trial highlight the potential benefits of intracranial nicardipine for aneurysmal subarachnoid hemorrhage (aSAH). This study aims to systematically identify the publication trends and research hotspots in this field through bibliometric analysis.</p><p><strong>Methods: </strong>Relevant publications were sourced from the Web of Science Core Collection (WoSCC). Bibliometric and visualization analyses were conducted using the online tools of the WoSCC database and CiteSpace 6.2.R6.</p><p><strong>Results: </strong>Analysis of 28 articles published by 158 researchers from 55 institutions across 8 countries revealed an intermittent small-scale growth in annual publication volume from 1994 to 2024, with a continuous rise in annual citation volume since 2005, indicating growing interest in the field. Japan, Germany, and the United States of America (USA) were the most prolific and influential countries. Institutions such as Tokyo Women's Medical University showed particularly significant contributions. Kasuya Hidetoshi was the most prolific author. There was little global collaboration among countries, institutions, and authors, with distinct regional research characteristics: Japan and Germany focused on intracranial implants, while the USA concentrated on intrathecal injections. Major publishing and co-cited journals included <i>Neurocritical Care, Acta Neurochirurgica, Journal of Neurosurgery</i>, and <i>Stroke</i>. Popular keywords in 2024 included \"preventing cerebral vasospasm\", \"delayed cerebral ischemia\", \"outcome events\", and \"clinical trials\", revealing current research hotspots.</p><p><strong>Conclusion: </strong>This study maps the global clinical research landscape of intracranial application of nicardipine for aSAH from 1994 to 2024, providing valuable references and guidance for future research.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1129-1146"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medication Safety in Intravenous Therapy: Compatibility of Etoposide with Frequently Drugs Used in Tumour Critical Care During Simulated Y-Site Administration.","authors":"Haiwen Ding, Tong Tong, Sheng Liu, Liqin Tang, Zhaolin Chen","doi":"10.2147/DDDT.S489534","DOIUrl":"10.2147/DDDT.S489534","url":null,"abstract":"<p><strong>Objective: </strong>Etoposide is an antineoplastic agent widely used to treat pediatric and adult cancers. Critically ill patients are expected to receive several intravenous pharmaceutical drugs while admitted to hospitals. When compatibility data are available, intravenous drugs may be administered simultaneously through the Y-site. This study aimed to determine the compatibility of etoposide during simulated Y-site administration with 45 continuous-infusion drugs that are commonly administered in tumor critical care units.</p><p><strong>Methods: </strong>Etoposide was diluted to a concentration of 0.25 mg/mL in 0.9% sodium chloride (NS) and other intravenously tested drugs were reconstituted according to the manufacturer's recommendations to the final clinical desired concentrations. Y-site administration was simulated in vitro by mixing 5 mL etoposide with other diluted intravenous medications under aseptic conditions in a 1:1 ratio. Compatible solutions were withdrawn at certain time intervals (0, 1, 2, 4 hours) after mixing and tested visually, using a Tyndall beam, pH, turbidity, insoluble particles, and UV absorption as measures of compatibility.</p><p><strong>Results: </strong>Etoposide was compatible with 38 (84%) of the 45 drugs tested within four hours. Glutathione and human granulocyte colony-stimulating factor immediately showed incompatibility with etoposide. Within 1 h, four medications (cefuroxime sodium, ilaprazole sodium, mycophenolate, and xuebijing) were incompatible. Within 4 h, one medications (ceftazidime) were also found to be incompatible with etoposide under observation.</p><p><strong>Conclusion: </strong>Seven of the 45 common medications in tumor critical care tested with etoposide were incompatible within 4 h. If co administration is inevitable and the drug is infused through a port catheter, a larger volume of saline (NS) or dextrose 5% in water (D5W) should be used to flush the port catheter before and after the etoposide infusion to clean the lumen of the port catheter.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1147-1161"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib Monotherapy Versus Lenvatinib in Combination with PD-1 Blockades as Re-Challenging Treatment for Patients with Metastatic Osteosarcoma: A Real-World Study.","authors":"Guohui Song, Qinglian Tang, Jinchang Lu, Huaiyuan Xu, Anqi Wang, Chuangzhong Deng, Hao Wu, Jinxin Hu, Xiaojun Zhu, Jin Wang","doi":"10.2147/DDDT.S501742","DOIUrl":"10.2147/DDDT.S501742","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the efficacy and safety of lenvatinib, either as a monotherapy or in combination with programmed death-1 (PD-1) blockades, as re-challenging treatment in patients with metastatic osteosarcoma following treatment failure with previous tyrosine kinase inhibitors (TKIs).</p><p><strong>Patients and methods: </strong>We retrospectively reviewed the data of 26 patients with metastatic osteosarcoma who received rechallenge treatment with lenvatinib monotherapy or lenvatinib plus PD-1 blockades after failure of the initial TKI treatment from January 2020 to June 2024 in our center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), and safety.</p><p><strong>Results: </strong>Of the 26 patients, ORR and CBR were 11.5% and 61.5%, respectively. The median duration of follow-up was 15 months (range, 4.3-25.6) with a median PFS of 7.2 months (95% CI: 1.9-12.5). A total of 14 patients received lenvatinib as a monotherapy, and 12 received a combination therapy of lenvatinib and PD-1 blockade. No significant differences were observed in ORR (0 vs 25%) and CBR (57.1 vs 66.7%) between the two groups. Additionally, the combination cohort exhibited a significantly longer PFS compared to the monotherapy cohort (8.6 [95% CI: 5.0-12.1] vs 4.0 months [95% CI: 1.0-7.0], <i>p</i> = 0.022). 96.2% of patients experienced grade 1 or more adverse events (AEs). Grade 3 adverse events occurred in 6 (23.1%) patients. The safety profiles of the lenvatinib and PD-1 blockade combination group were found to be comparable to those of the lenvatinib monotherapy group.</p><p><strong>Conclusion: </strong>Our data indicated that patients with metastatic osteosarcoma could potentially benefit from lenvatinib rechallenge after progress with initial TKI treatment. The combination of lenvatinib and PD-1 blockade therapy demonstrated promising survival outcomes in patients with metastatic osteosarcoma, accompanied by a manageable toxicity profile.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1119-1128"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Propranolol Hydrochloride Formulations for the Treatment of Infantile Hemangiomas.","authors":"Lin Ren, Xiaowen Xu, Xianbin Liu, Hong Ning, Qian Ding, Min Yang, Tiantian Liang","doi":"10.2147/DDDT.S496847","DOIUrl":"10.2147/DDDT.S496847","url":null,"abstract":"<p><p>Infantile hemangiomas (IHs) are a kind of skin soft tissue benign tumors in infants, with a high incidence rate and significant harm. Rapid early proliferation can cause severe cosmetic deformities and organ development disorders. Propranolol Hydrochloride (PRH), a non-selective adrenergic β-receptor blocker, has become the first-line treatment for IHs due to its good efficacy and safety compared to other drugs. To further improve the bioavailability of PRH, deliver it more safely and effectively to the lesion site, and enhance patient compliance, researchers are continually developing new PRH formulations for the treatment of IHs. This article briefly introduced the pathogenesis of IHs and the therapeutic mechanism of PRH. It also provided a detailed overview of various new PRH formulations developed over the past 12 years for the treatment of IHs, including improved oral formulations, topical creams, gels, liposomes/nanoparticles, transdermal patches, microneedles, and targeted injectable formulations. This article summarized the development prospects and technical challenges of these new formulations. It aims to provide a comprehensive review of recent advances in new propranolol formulations and technologies for treating IHs, offering a reference for further research and application. At the same time, it is hoped that various new formulations of PRH can be safely and efficiently used in clinical practice in the future.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1163-1183"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining Network Pharmacology, Molecular Docking and Experimental Validation to Explore the Effects and Mechanisms of Indirubin on Acute Lymphoblastic Leukemia.","authors":"Lu Jin, Yunshuang Guan, Xue Li, Mingyue Wang, Ying Shen, Nianxue Wang, Zhixu He","doi":"10.2147/DDDT.S500249","DOIUrl":"10.2147/DDDT.S500249","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the effects and underlying mechanisms of indirubin in treating ALL using network pharmacology and experimental validation.</p><p><strong>Methods: </strong>Potential targets of indirubin- and ALL-related genes were identified using public databases. Core genes were filtered through protein-protein interaction analysis in Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to explore the potential mechanisms of indirubin against ALL. Drug-disease-functional annotation-signaling pathway network maps were constructed. Molecular docking between indirubin and core proteins was performed using AutoDock Vina software. Finally, both in vitro and in vivo experiments were performed to validate these findings.</p><p><strong>Results: </strong>PPI network analysis identified eight potential core targets of indirubin in ALL: AKT1, CASP3, and the mammalian target of rapamycin. GO and KEGG enrichment analyses suggested that the mechanism of action of indirubin against ALL involves multiple biological functions and signaling pathways, with the PI3K-AKT pathway likely playing a central role. Molecular docking findings further confirmed the strong binding affinity of indirubin for the core targets. Both in vitro and in vivo experiments demonstrated that indirubin inhibited ALL cell proliferation and induced cell cycle arrest and apoptosis; the underlying mechanism may involve the PI3K-AKT signaling pathway.</p><p><strong>Conclusion: </strong>The action and mechanism of indirubin in ALL through network pharmacology, as well as in vivo and in vitro experimental validation were elucidated, offering new insights and potential therapeutic avenues for the treatment of ALL.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1083-1103"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}