Chemico-Biological Interactions最新文献

{"title":"Corrigendum to “Design, synthesis, and antitumor activity of PLGA nanoparticles incorporating a discovered benzimidazole derivative as EZH2 inhibitor” [Chem.-Biol. Interact. 344 (2021) 109530]","authors":"Hoda A. Elkot , Ibrahim Ragab , Noha M. Saleh , Mohamed N. Amin , Sara T. Al-Rashood , Shahenda M. El-Messery , Ghada S. Hassan","doi":"10.1016/j.cbi.2026.111959","DOIUrl":"10.1016/j.cbi.2026.111959","url":null,"abstract":"","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"429 ","pages":"Article 111959"},"PeriodicalIF":5.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial and multi-omics transcriptomic dissects platinum resistance in lung adenocarcinoma: a five-gene predictive model with tumor microenvironment dynamics","authors":"Jie Chen ,&nbsp;Yixin Chen ,&nbsp;Yi Lu ,&nbsp;Yuyu He ,&nbsp;Feng Jiang ,&nbsp;Lijuan Hu ,&nbsp;Yumin Wang","doi":"10.1016/j.cbi.2026.111952","DOIUrl":"10.1016/j.cbi.2026.111952","url":null,"abstract":"<div><div>The scarcity of reliable biomarkers and predictive models for platinum resistance in lung adenocarcinoma (LUAD) poses a significant clinical challenge. This study endeavors to identify molecular subtypes related to platinum resistance and construct a robust predictive model through multi-omics techniques.</div><div>We performed integrative analysis of public datasets using advanced bioinformatics strategies, including spatial transcriptome deconvolution and consensus clustering. Bulk RNA deconvolution analysis was conducted to characterize tumor microenvironment heterogeneity. Feature selection was performed using the Supervised Principal Component (SuperPC) algorithm, followed by diagnostic model construction validated through receiver operating characteristic (ROC) analysis. Functional validation was performed through cytological experiments measuring cisplatin IC50 alterations following gene manipulation in LUAD cell lines.</div><div>Consensus clustering revealed distinct LUAD subtypes, with Cluster1 demonstrating significant platinum resistance. We first subtyped the patients in the bulk transcriptome data based on consistency clustering, and then analyzed the differences between different platinum-resistant subtypes (Cluster 1 and Cluster 2), so as to screen 333 isotype-specific differentially expressed genes and 15 platinum resistance-related (PRR) genes were selected through machine learning. A refined 5-gene signature (ANKRD29/CACNA2D2/DSP/HSD17B6/SPP1) achieved exceptional predictive performance (AUC = 0.9639). Spatial transcriptomics demonstrated compartmentalized expression patterns: SPP1/DSP localized to tumor niches, HSD17B6/CACNA2D2 to epithelial regions, and ANKRD29 depletion in stromal areas. Cellular colocalization analysis revealed malignant epithelial PH proximity to myeloid and mast cells. Functional validation confirmed that ANKRD29/CACNA2D2 overexpression sensitized A549/DDP cells to cisplatin, while DSP/SPP1/HSD17B6 overexpression induced resistance. Experiments in nude mice have shown that these genes are closely related to cisplatin resistance in LUAD.</div><div>This study identifies the Cluster1 subtype and malignant epithelial PH as crucial determinants of platinum resistance in LUAD. Our innovative 5-gene predictive model exhibits clinical-grade diagnostic accuracy, and spatial transcriptomic characterization offers mechanistic insights into the dynamics of the tumor microenvironment.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"429 ","pages":"Article 111952"},"PeriodicalIF":5.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyflumetofen induces hepatic steatosis and disrupts lipid metabolism in zebrafish larvae","authors":"Wei-Guo Wang ,&nbsp;Yi-Min Duan ,&nbsp;Da-Wei Yan ,&nbsp;Lan Xu ,&nbsp;Wen-Ping Xu ,&nbsp;Li-Ming Tao ,&nbsp;Yang Zhang ,&nbsp;Jia-Gao Cheng","doi":"10.1016/j.cbi.2026.111957","DOIUrl":"10.1016/j.cbi.2026.111957","url":null,"abstract":"<div><div>Cyflumetofen is a highly effective acaricide, and both it and its metabolites are often present in the environment as pollutants. Therefore, the safety of cyflumetofen for non-target organisms requires further attention. This study used zebrafish larvae to evaluate the effects of cyflumetofen on liver development. After 72-h exposure, cyflumetofen specifically manifested as significantly reduced liver area and histological damage (cellular vacuolization, nuclear loss) in the 2.0 and 4.0 μg/mL exposure groups. Concurrently, Oil Red O, Nile Red, and BODIPY 493/503 staining all showed that cyflumetofen induced hepatic and systemic lipid accumulation, accompanied by increased levels of TG, CH, FC, and LDL-C, and decreased HDL-C levels. qPCR analysis further revealed the molecular mechanism by which it disrupts lipid metabolism: promoting the expression of fatty acid synthesis genes (<em>srebp-1c</em>, <em>fas</em>) and inhibiting the expression of catabolism genes (<em>cpt-1a</em>, <em>pparα</em>) and lipid transport (<em>fabp2</em>). These integrated results demonstrate that cyflumetofen can cause abnormal liver development and induce systemic lipid metabolism disorder in zebrafish larvae.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"429 ","pages":"Article 111957"},"PeriodicalIF":5.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxicity and mechanism of metal and metal oxide nanoparticles","authors":"Shouying Cao ,&nbsp;Meng Tang ,&nbsp;Changcun Bai","doi":"10.1016/j.cbi.2026.111953","DOIUrl":"10.1016/j.cbi.2026.111953","url":null,"abstract":"<div><div>Metal and metal oxide nanoparticles, owing to their unique physicochemical properties, have been extensively applied in biomedicine, cell labeling and sorting, drug delivery, and clinical therapy. Their impact on human health and environmental safety is increasingly drawing attention. These nanoparticles can enter the nervous system through multiple pathways, triggering the release of reactive oxygen species and cytokines, leading to blood-brain barrier damage and central nervous system dysfunction. This paper includes a methods section detailing literature search strategies, screening criteria, and time windows. It explores pathways for metal and metal oxide nanoparticles to enter the nervous system and their neurotoxic effects <em>in vivo</em> and <em>in vitro</em>. The influence of developmental stage and gender differences on the neurotoxicity of metal and metal oxide nanoparticles is clearly articulated. It systematically reviews and critically compares key molecular and cellular mechanisms underlying neurotoxicity induced by different types of metal and metal oxide nanoparticles, revealing their intrinsic connections and cascading effects. It critically evaluates particle effects versus ionic effects and grades the strength of particle-specific toxicity evidence. Factors influencing the toxicity of metal and metal oxide nanoparticles, including particle size, exposure concentration, and solubility are discussed. The neurotoxic characteristics and potential unique mechanisms distinguishing these nanoparticles from other nanomaterials are clarified. Possible mechanisms of neurotoxicity and physicochemical factors influencing toxicity are summarized, exploring how physicochemical properties determine interactions with the nervous system and toxicity severity. This review concludes by identifying existing challenges and future research directions regarding the neurotoxic effects of metal and metal oxide nanoparticles, providing a reference framework for their safety assessment and neurotoxicity studies.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"428 ","pages":"Article 111953"},"PeriodicalIF":5.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamic acid induces neurodevelopmental defects via PPARγ signaling in zebrafish","authors":"Lixia Peng ,&nbsp;Haoxu Wang ,&nbsp;Yafang Li ,&nbsp;Xiaoyu Liu ,&nbsp;Kaihui Chang ,&nbsp;Wenxin Yi ,&nbsp;Baokun Wang ,&nbsp;Nan Zeng ,&nbsp;Zhiqiang Li ,&nbsp;Chuanhong Wu","doi":"10.1016/j.cbi.2026.111929","DOIUrl":"10.1016/j.cbi.2026.111929","url":null,"abstract":"<div><div><em>Cinnamomum cassia</em> Presl is traditional used to warm the body, dispel cold and relieve pain in China. It is a commonly used traditional Chinese medicine and spice in daily heath care. Cinnamic acid (CA) is one of the main active compounds isolated from cinnamon bark. In the present study, we found that CA (4 mg/L and 8 mg/L) caused neurodevelopment defects in zebrafish as evidenced by shortened body length, trunk curvature, behavioral abnormalities and increased mortality. And we explored the potential targets and biological mechanisms of neurotoxicity caused by cinnamic acid using network toxicology and zebrafish experiments. 154 CA related target genes were shared with neurotoxicity-related genes. Using different algorithms in Cytoscape software, 4 key target genes were finally identified as TNF, CASP3, IL6 and PPARG, which were further confirmed with molecular docking. For the next, we confirmed these targets in zebrafish. CA up-regulated <em>tnf-α</em>, <em>il-6</em> and <em>casp</em><em>ase</em><em>3</em> gene expressions, and down-regulated <em>pparg</em> gene expression. Moreover, it can inhibit the activity of AChE, ATPases, CAT and SOD, decreased neuronal fluorescence, and increased macrophages and neutrophile granulocytes, ROS and MDA. In addition, it could induce apoptosis and abnormal neurodevelopmental-related gene expression in zebrafish larvae. Oxidative stress inhibitor astaxanthin could ameliorate the behavioral impairment and the expression of neurodevelopment-related genes. Moreover, when PPAR-γ expression was increased, the behavioral impairment, inflammatory response, oxidative stress, and apoptosis levels were alleviated. All these data demonstrated that the developmental neurotoxicity of CA in zebrafish might be attributed to PPAR-γ mediated oxidative stress, inflammatory response and apoptosis.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111929"},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH5-mediated autophagic flux impairment is involved in bilirubin neurotoxicity","authors":"Jinfu Zhou ,&nbsp;Sining Liao ,&nbsp;Chenran Zhang ,&nbsp;Guilin Li ,&nbsp;Fuli Zheng ,&nbsp;Guangxia Yu ,&nbsp;Hong Hu ,&nbsp;Wenya Shao ,&nbsp;Zhenkun Guo ,&nbsp;Siying Wu ,&nbsp;Jianping Tang ,&nbsp;Huangyuan Li","doi":"10.1016/j.cbi.2026.111940","DOIUrl":"10.1016/j.cbi.2026.111940","url":null,"abstract":"<div><div>Bilirubin-induced brain damage represents a serious clinical consequence of hyperbilirubinemia, yet the role and underlying molecular mechanisms of autophagy the remain largely elusive. Here, we demonstrate that, for the first time, N6-methyladenosine (m6A) demethylase AlkB homolog 5 (ALKBH5) mediated dysregulated autophagic flux contributes to bilirubin-induced neurotoxicity. Hyperdifferential differentiated PC12 cells and neonatal Sprague-Dawley rats were employed as in vitro and in vivo models, respectively. <em>In vivo</em> experiments first showed a dysregulated autophagy and neuronal damage in hyperbilirubinemia. <em>In vitro</em> further experiments observed that bilirubin exposure inhibited autophagy as illustrated by the downregulated p62 and LC3-II protein expression and transmission electron microscopy results. Furthermore, we found that the autophagic flux impairment was due to the inhibition of initial stage following bilirubin exposure, which was pharmacologically validated using rapamycin and bafilomycin A1 and up-regulated protein expression of <em>p</em>-mTOR and BCL2. More importantly, we found that ALKBH5 overexpression can exacerbate bilirubin-induced autophagic flux damage, whereas ALKBH5 knockdown attenuated the inhibited autophagic flux damage. Mechanistically, Vacuole membrane protein 1 (VMP1), Ras-related GTP-binding protein C (RRAGC), and protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1) were identified as the target genes of ALKBH5 to impair autophagic flux with mRNA stability assay, RT-PCR analysis, and bioinfomatic analysis, thereby promoting bilirubin-induced neurotoxicity. Collectively, our findings reveal that ALKBH5 participates in bilirubin-induced autophagic flux impairment, and propose m6A-dependent autophagy as a potential therapeutic target in hyperbilirubinemia.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111940"},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol-induced alterations in selected electrokinetic properties of in vitro models: LN-18 glioma cells and PC liposomes","authors":"Joanna Kotyńska ,&nbsp;Agnieszka Owerczuk ,&nbsp;Monika Naumowicz","doi":"10.1016/j.cbi.2026.111933","DOIUrl":"10.1016/j.cbi.2026.111933","url":null,"abstract":"<div><div>Resveratrol (RSV) has received widespread attention due to its diverse biological activities, including antioxidant, cardioprotective, and antitumor. Numerous preclinical investigations have revealed the anticancer action of resveratrol in various tumor types, including gliomas. This polyphenol is characterized by low water solubility and a high membrane partition coefficient, suggesting a strong affinity for the lipid components of biomembranes. Consequently, biomembranes are a prime target for resveratrol. However, its interactions with membrane lipids and precise localization within the cell membrane remain unclear and subject to debate. In this study, we investigated the electrokinetic behaviour of phosphatidylcholine (PC) liposomes and LN-18 human glioblastoma cells under the influence of resveratrol. Using the electrophoretic light scattering method, we monitored changes in electrokinetic (zeta) potential and membrane surface charge of both the <em>in vitro</em> models as a function of pH. Furthermore, we employed the MTT assay to assess the viability of RSV-treated cells. The measurements revealed the dose-dependent effects of RSV on the analyzed parameters of both liposomes and cells. Theoretical parameters, including surface concentrations of membrane groups and association constants, were derived through quantitative analysis of adsorption equilibria to characterize the binding of solution ions to glioblastoma cell membranes. Integrating theoretical insights with experimental findings is essential for a more comprehensive interpretation of the results.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111933"},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thalidezine triggers Cathepsin B-mediated cell death in T-cell lymphoma by disrupting lysosomal function","authors":"Yingjie Qing ,&nbsp;Su Xu ,&nbsp;Dawei Yang ,&nbsp;Jie Liu ,&nbsp;Hui Cao","doi":"10.1016/j.cbi.2026.111932","DOIUrl":"10.1016/j.cbi.2026.111932","url":null,"abstract":"<div><div>T-cell lymphoma (TCL) is an aggressive malignancy defined by poor prognosis and therapeutic resistance, demanding innovative strategies. Targeting the lysosome to induce cell death has emerged as a powerful anti-cancer strategy, however its potential as a therapeutic target in TCL is yet to be fully developed. Here we report that Thalidezine (Tha) is a new and highly selective lysosomotropic agent (LA) with strong activity against TCL. Thalidezine diminished the acidic pH, and more importantly, induced the lysosomal membrane permeabilization (LMP). This LMP was not a passive event; it triggered the immediate and critical release of the protease Cathepsin B (CTSB) from the lysosomal lumen. We demonstrate that this cytosolic CTSB is the key executioner, directly initiating the apoptotic cascade through caspase-3 activation. Remarkably, CTSB knockdown rescued TCL cells from Tha-induced death, confirming that the CTSB-caspase axis constitutes the major death axis. Furthermore, Tha demonstrated significant <em>in vivo</em> efficacy in TCL cells-bearing <em>NOD/SCID</em> mice. In conclusion our results reveal Tha is a novel potent drug candidate and uncover a defined mechanism by weaponizing lysosomes to release CTSB, thereby establishing a therapeutically relevant vulnerability in TCL.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111932"},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent effects of early-life paracetamol exposure on behavior and monoamines in the rat central nervous system","authors":"Filip Górawski,&nbsp;Ilona Joniec-Maciejak,&nbsp;Agnieszka Piechal,&nbsp;Justyna Pyrzanowska,&nbsp;Dagmara Mirowska-Guzel,&nbsp;Kamilla Blecharz-Klin","doi":"10.1016/j.cbi.2026.111937","DOIUrl":"10.1016/j.cbi.2026.111937","url":null,"abstract":"<div><div>The effects of prenatal and early postnatal paracetamol exposure on behavior and neurotransmission in offspring remain poorly understood. The aim of this study was to investigate the consequences of paracetamol administration during fetal and early postnatal development period in rats. A total of 43 offspring prenatally exposed to paracetamol were assigned to experimental groups based on dose (10 or 30 mg/kg b.w.) and stratified by sex.</div><div>Paracetamol was administered throughout the entire prenatal period and during the first three months of postnatal life, with treatment continuing during the behavioral assessments. These included the Novel Object Recognition test, Staircase test, Hole Board, and Morris Water Maze, which were conducted to evaluate exploratory behavior, motor function, anxiety, and memory.</div><div>Neurochemical analyses of neurotransmitters level in forebrain regions (prefrontal cortex, hippocampus, hypothalamus, striatum), hindbrain regions (cerebellum, medulla oblongata), and spinal cord were performed using high-performance liquid chromatography (HPLC).</div><div>The behavioral response to paracetamol differed between sexes. Paracetamol exposure enhanced exploration and produced a moderate anxiolytic effect, which was more pronounced in females and increased dose-dependently. Furthermore, sex-dependent impairments in spatial memory recall were observed in the Water Maze test, particularly in females exposed to paracetamol.</div><div>Biochemically, paracetamol exposure led to significant changes in dopaminergic and noradrenergic systems between the sexes, particularly in the hypothalamus (e.g., increased noradrenaline and dopamine turnover and their metabolites in males) and medulla oblongata (e.g. decreased noradrenalin turnover in males) indicating a sex-specific neurochemical response. These findings suggest that paracetamol exposure during critical developmental periods may influence cognitive function and neurotransmitter regulation in a sex-dependent manner, with female and male offspring demonstrating different neurobehavioral outcomes.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111937"},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular actions of sepantronium bromide (YM155) on survivin-dependent cell death in cancer and beyond","authors":"Steffanni S.A. Marques ,&nbsp;Mateus E.T. Oliveira ,&nbsp;Édipo G. França-Lara ,&nbsp;Caroline K. Menuzzi ,&nbsp;Adrielle S. Oliveira ,&nbsp;Melissa A. Santos ,&nbsp;Luciana F.C.M. Zischler ,&nbsp;Andrea N. Moreno-Amaral ,&nbsp;Selene Elifio-Esposito","doi":"10.1016/j.cbi.2026.111951","DOIUrl":"10.1016/j.cbi.2026.111951","url":null,"abstract":"<div><div>Sepantronium bromide (YM155) emerged as one of the earliest small molecules designed to selectively suppress survivin (BIRC5), a key regulator of apoptosis and cell-cycle progression in cancer. Over the past two decades, YM155 has provided a unique translational framework to investigate the molecular crosstalk between survivin, cellular stress responses, and therapy resistance that shape cell-death outcomes. This mini-review integrates preclinical and clinical data to delineate how YM155 modulates transcriptional networks, mitochondrial integrity, DNA damage signaling, and autophagy. Particular attention is given to adaptive redox and metabolic programs that limit its efficacy in solid and hematological tumors. The article also revisits the outcomes of early clinical trials, highlighting both the safety profile and the challenges that hindered durable patient responses. Beyond oncology, emerging findings have repositioned YM155 as a probe to interrogate survivin-regulated processes in vascular and immune pathologies. By bridging molecular and clinical evidence, this review contextualizes YM155 within the broader landscape of targeted small molecules, emphasizing its value as a model for developing next-generation survivin modulators and precision-based therapeutic strategies.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"427 ","pages":"Article 111951"},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}