International journal of molecular medicine最新文献

{"title":"[Expression of Concern] ISL1 promotes cancer progression and inhibits cisplatin sensitivity in triple‑negative breast cancer cells.","authors":"Yang Zhang, Lu Wang, Peng Gao, Zhiguo Sun, Ning Li, Yanqin Lu, Jianglun Shen, Jian Sun, Yiming Yang, Hao Dai, Haifeng Cai","doi":"10.3892/ijmm.2026.5846","DOIUrl":"https://doi.org/10.3892/ijmm.2026.5846","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell invasion assay experiments shown in Fig. 3A, B and C on p. 2348, two pairs of data panels were overlapping, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. In addition, an independent investigation of the data in this paper undertaken by the Editorial Office revealed that flow cytometric data in Fig. 4A were shared with a paper that was published in the journal <i>OncoTargets and Therapy</i> featuring no authors in common (which was received at that journal one month after the submission of the above paper to <i>International Journal of Molecular Medicine</i>), and flow cytometric data in Fig. 5C were shared with a different paper also having no authors in common that was subsequently submitted to the journal <i>Oncology Reports</i>. The authors have been contacted by the Editorial Office to offer an explanation for the issues described above, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 42: 2343‑2352, 2018; DOI: 10.3892/ijmm.2018.3842].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation beyond the plasma membrane: How secretory pathway kinases sculpt the cellular dialogue in cancer (Review).","authors":"Ziang Geng, Shu Guan, Shaoqi Du, Shuo Zhang, Jiaxin Hao, Siyuan Tian, Chen Zhu, Shaonan Du","doi":"10.3892/ijmm.2026.5845","DOIUrl":"https://doi.org/10.3892/ijmm.2026.5845","url":null,"abstract":"<p><p>Intercellular communication is critical for tissue homeostasis, development and immune responses, with its disruption often implicated in various diseases, particularly cancer. Secretory pathway kinases and kinase‑like proteins (SPKKPs) constitute a distinctive enzyme class operating within the luminal secretory pathway or extracellular space, positioning them as pivotal regulators of cellular communication. This review consolidates current insights into the role of SPKKPs, including the FAM20 family, four‑jointed box kinase 1 (FJX1) and others, in orchestrating intercellular interactions through the phosphorylation of secreted proteins, extracellular matrix components and extracellular vesicle (EV) cargo. The molecular mechanisms by which SPKKPs modulate key oncogenic signaling pathways, such as PI3K/AKT, ERK/MAPK and SMAD family member 2, across diverse cancer types are examined. Additionally, their involvement in EV‑mediated signaling, extracellular matrix remodeling and regulation of fundamental biological processes, including development, tissue homeostasis and immune coordination, is explored. The review further addresses SPKKP dysregulation in a range of pathologies, from nervous system tumors to gastrointestinal and reproductive cancers, and discusses emerging therapeutic strategies. These strategies include specific kinase inhibitors, FJX1‑targeted peptide vaccines and innovative approaches targeting exosomes carrying SPKKPs substrates. Ultimately, this work highlights the essential role of SPKKPs in intercellular communication networks and their promising potential as diagnostic biomarkers and therapeutic targets, particularly in cancer.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligustroflavone protects against acute kidney injury by inhibiting ferroptosis via acting on GSK3β/NRF2 signaling.","authors":"Jiayu Song, Long Wang, Yaru Wang, Jie Meng, Jingyi Sheng, Yongfeng Zhao, San Yan Xu, Juan Lei, Fangfang Cai, Yunwen Yang","doi":"10.3892/ijmm.2026.5841","DOIUrl":"10.3892/ijmm.2026.5841","url":null,"abstract":"<p><p>Ferroptosis exerts a recognized role in the pathogenesis of acute kidney injury (AKI) and is considered a critical target for improving its prognosis. Emerging evidence indicates that ferroptosis serves a pivotal role in pathogenesis of AKI and targeting ferroptosis provides a promising therapeutic strategy in treatment of AKI. In the present study, ligustroflavone (LIG), which is a flavonoid with oral activity extracted from <i>Ligustrum lucidum</i>, was found to inhibit ferroptosis through activation of nuclear factor erythroid 2‑related factor 2 (NRF2) via inhibition of GSK3β <i>in vivo</i> and <i>in vitro</i>.<i> In vivo</i>, cisplatin (CDDP) and ischemia‑reperfusion injury (IRI)‑induced murine models of AKI were constructed to evaluate the possible effects of LIG. <i>In vitro</i>, the protective effects of LIG were assessed in cultured mouse renal proximal tubular epithelial cells (TKPTs). Immunostaining, reverse transcription‑quantitative PCR, western blot and lipid peroxidation assays were performed to detect renal tubular injury and ferroptosis. The results of the present study demonstrated that LIG administration significantly ameliorated CDDP or IRI induced renal damage in mice. Additionally, administration of LIG significantly ameliorated lipid peroxide accumulation and inhibited ferroptosis in the kidneys of AKI mice. <i>In vitro</i>, LIG treatment markedly ameliorated CDDP‑induced lipid peroxidation and ferroptosis in cultured TKPTs via GSK3β inhibition and NRF2 activation. Furthermore, knockout of GSK3β also protected against CDDP‑induced cell death and LIG exerted no additional protective effects in GSK3β‑knockout TKPTs. Together, the present findings offer a new potential strategy for AKI therapies by targeting ferroptosis.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress.","authors":"Ken Takebe, Takayuki Nishiyama, Shinya Hayashi, Shingo Hashimoto, Takaaki Fujishiro, Noriyuki Kanzaki, Kohei Kawakita, Kenjiro Iwasa, Ryosuke Kuroda, Masahiro Kurosaka","doi":"10.3892/ijmm.2026.5843","DOIUrl":"10.3892/ijmm.2026.5843","url":null,"abstract":"<p><p>Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that, regarding the caspase‑9 and cleaved caspase‑9 bands in Fig. 5D on p. 333, the bands shown for the '10% 0h' and the '10% 12h' lanes/experiments were strikingly similar, albeit with a small downwards displacement of the cleaved caspase‑9 band in the right‑hand lane of the gel compared with the left‑hand lane. A visual inspection of this figure part also revealed the probable presence of breaks in continuity in the affected gel slices, comparing the left‑ and the right‑hand lanes. Given that this issue has come to light, the Editor of <i>International Journal of Molecular Medicine</i> has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in these data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any inconvenience caused, and we thank the reader for drawing this matter to our attention. [International Journal of Molecular Medicine 27: 329‑335, 2011; DOI: 10.3892/ijmm.2010.588].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin attenuates ferroptosis in diabetic nephropathy through activation of the Nrf2/HO‑1 signaling pathway.","authors":"Hanshuang Liu, Xiaoxiao Zhang, Yubing Cui, Shengxi Xiong, Linjuan Huang, Min Li, Chen Shao, Xiaolei Hu","doi":"10.3892/ijmm.2026.5842","DOIUrl":"10.3892/ijmm.2026.5842","url":null,"abstract":"<p><p>Renal tubular injury has emerged as a critical determinant in the pathogenesis of diabetic nephropathy (DN). Ferroptosis, a recently characterized mode of iron‑dependent regulated cell death, has been implicated in the development of renal tubular damage. Dapagliflozin (DAPA), a sodium‑glucose cotransporter 2 inhibitor, has demonstrated efficacy in attenuating DN progression and preserving renal function. The present study sought to elucidate the inhibitory mechanisms by which DAPA modulates ferroptosis in DN. To this aim, the expression profiles of key molecular markers within the ferroptosis cascade were systematically evaluated using 6‑week‑old male C57BL/6J mice and high‑glucose‑cultured human renal tubular epithelial cells as experimental models. The findings revealed that DAPA notably ameliorated renal histopathological alterations, upregulated the expression of solute carrier family 7 member 11, glutathione peroxidase 4 and ferritin heavy chain 1, whilst concomitantly downregulating transferrin receptor 1. These effects were mediated through the activation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) in C57BL/6J mice. Collectively, these data indicate that the reno‑protective effects of DAPA in DN may be attributable to the suppression of ferroptosis via activation of the Nrf2/HO‑1 signaling axis.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in understanding the NLRP3 inflammasome‑mediated mechanisms and therapeutic targets in diabetic nephropathy (Review).","authors":"Xiwei Wang, Shuang Li, Xiaotian Ge, Tao Xie, Sainan Li, Ruiqi Yuan, Tianxi Li, Hui Yuan","doi":"10.3892/ijmm.2026.5847","DOIUrl":"https://doi.org/10.3892/ijmm.2026.5847","url":null,"abstract":"<p><p>Diabetic nephropathy (DN), a severe microvascular complication of diabetes, has exhibited a steadily increasing global incidence and is a major contributor to diabetes‑related morbidity and mortality. DN is characterized by glomerular sclerosis, podocyte loss, tubular atrophy and excessive extracellular matrix deposition, among other features. The pathogenesis of DN is complex, involving multiple pathological processes, with the inflammatory cascade recognized as the core driver of its progression. Abnormal activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key component of the innate immune system, can trigger pyroptosis and thereby aggravate renal injury. Whilst current literature primarily describes isolated mechanisms of DN, the present review summarizes the pathogenesis of DN and the NLRP3 inflammasome‑related signaling pathways, proposing a novel three‑tier hierarchical regulatory framework (upstream priming, midstream activation and downstream execution) for the five core NLRP3‑related signaling pathways in DN, and systematically dissects the mitochondrial metabolic‑cGAS‑STING synergistic mechanism that drives NLRP3 activation, thus addressing the research gap in metabolic‑immune crosstalk in DN. Furthermore, potential therapeutic agents targeting the NLRP3 inflammasome are discussed, and targeted therapeutic strategies stratified according to <i>in vivo</i> and <i>in vitro</i> validation evidence (such as small‑molecule inhibitors, traditional Chinese medicine monomers/compounds and gene therapy) to provide a clear roadmap to clinical translation. Although current research on DN is limited, the findings and analyses assessed in the present review provide valuable insights into its pathogenesis, treatment, prognosis and directions for future experimental studies.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis in musculoskeletal disorders: Emerging mechanisms and therapeutic opportunities (Review).","authors":"Wenhui Gu, Haifeng Zhang, Lisha Ye, Fangming Liu, Ting Xu, Yinxian Yu, Guohua Wang","doi":"10.3892/ijmm.2026.5844","DOIUrl":"10.3892/ijmm.2026.5844","url":null,"abstract":"<p><p>Ferroptosis, an iron‑dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key mechanism underlying tissue degeneration and impaired regeneration in musculoskeletal disorders. Although ferroptosis is associated with conditions such as tendinopathy, sarcopenia, osteoarthritis and osteoporosis, systematic synthesis connecting molecular mechanisms with disease‑specific contexts and translational implications remains limited. The present review summarizes the fundamental molecular mechanisms of ferroptosis, including iron metabolism dysregulation, lipid peroxidation processes and antioxidant defense systems centered on GPX4 and glutathione. Subsequently, the involvement of ferroptosis across major musculoskeletal diseases was investigated, highlighting how iron imbalance, oxidative stress and age‑related alterations collectively contribute to tissue dysfunction and degeneration. Particular emphasis is placed on aging‑associated changes in iron homeostasis and antioxidant capacity as potential amplifiers of ferroptotic vulnerability in musculoskeletal tissues. Experimental modeling strategies and pharmacological modulation approaches used to investigate ferroptosis in musculoskeletal research are further discussed and their mechanistic relevance and translational challenges are analyzed. Finally, the present review outlines emerging therapeutic perspectives and future research directions aimed at improving the understanding and potential clinical targeting of ferroptosis in musculoskeletal disorders. By providing a structured and integrative synthesis, the present review clarifies the role of ferroptosis at the intersection of iron dysregulation, redox imbalance and musculoskeletal decline.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).","authors":"Siyuan Zhou, Yurong Jiang, Jixu Fan, Minjie Guo, Yi Wen, Chunhua Dai","doi":"10.3892/ijmm.2026.5848","DOIUrl":"https://doi.org/10.3892/ijmm.2026.5848","url":null,"abstract":"<p><p>Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑C motif chemokine ligand (CCL)2/CCR2 and CCL22/CCR4 that govern T‑cell trafficking and functional states. A map of organ‑specific cytokine programs that link therapeutic benefit and toxicity in the brain, lung, gastrointestinal tract, oral mucosa and liver is then provided, and actionable targets within inflammasome‑associated pyroptosis and fibrogenic cascades are highlighted. RT technical parameters, including fractionation, treatment volume, stereotactic body RT, Fast Linear Accelerator‑based Scanning Hybrid ultra‑high dose-rate delivery and proton therapy can differentially shape cytokine dynamics and modify the therapeutic window. The DNA damage response network with poly (ADP‑ribose) polymerase (PARP)1 as a central node represents a second hub that interfaces with antigen presentation and IFN signaling, supporting rational combinations with PARP inhibitors and immune checkpoint blockade. Finally, a translational algorithm with three pillars is proposed. The first pillar uses IFN‑related gene signatures and circulating cytokine profiles to stratify tumors by baseline IFN activity. The second pillar aligns RT timing with endogenous STING or IFN pulses and incorporates CCR2, CCR4 or colony stimulating factor 1 receptor blockade to counter myeloid cell‑mediated immunosuppression. The third pillar co‑manages treatment‑related toxicities by targeting the NLR family pyrin domain containing 3/gasdermin D axis or by using fibrosis‑modulating interventions. Furthermore, ongoing clinical trials of cytokine-directed agents combined with RT are summarized. This framework positions cytokines as measurable and modifiable variables for individualizing combined RT and immunotherapy.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] Differential regulation of the biosynthesis of glucose transporters by the PI3‑K and MAPK pathways of insulin signaling by treatment with novel compounds from <i>Liriope platyphylla</i>.","authors":"Yoen Kyung Lee, Ji Eun Kim, So Hee Nam, Jun Seo Goo, Sun Il Cho, Young Hwan Choi, Chang Jun Bae, Ong Min Woo, Jung Sik Cho, Dae Youn Hwang","doi":"10.3892/ijmm.2026.5840","DOIUrl":"https://doi.org/10.3892/ijmm.2026.5840","url":null,"abstract":"<p><p>Following the publication of the above article, an interested reader drew to the authors' attention that the β‑actin blots featured for the western blots in Figs. 5A and 8A were apparently the same, even though the samples came from different tissues (liver and brain, respectively). Upon re‑examining their original data, the authors have realized that the control blots were erroneously selected for Fig. 8A; moreover, the same processing error was made with the control blots for Fig. 6A (duplicated from those for Fig. 4A) and Fig. 9A (duplicated from Fig. 7A).  The revised versions of Figs. 6, 8 and 9, now showing the correct control western blots in Figs. 6A, 8A and 9A, are shown opposite and on the subsequent page. Note that the errors made in assembling these figures did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of <i>International Journal of Molecular Medicine</i> for granting them the opportunity to publish this. Furthermore, they apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 27: 319‑327, 2011; DOI: 10.3892/ijmm.2010.581].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"58 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Hsp90 inhibitor JD‑02 inhibits HSV‑1 infection via the Raf/MEK/ERK signaling pathway.","authors":"Yexuan Zhu, Xiaohui Wang, Jiaying Lin, Xiao Wang, Kai Zheng, Zhe Ren, Ji Xiao, Yifei Wang","doi":"10.3892/ijmm.2026.5810","DOIUrl":"10.3892/ijmm.2026.5810","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV‑1) is a neurotropic pathogen with an extremely high infection rate. The excessive use of acyclovir (ACV) and nucleoside analogs has resulted in the emergence of drug‑resistant HSV‑1 strains, thereby underscoring the need for the development of novel therapeutic agents against HSV‑1. The present study sought to evaluate the efficacy and elucidate the mechanism of action of the novel Hsp90 inhibitor, JD‑02, in the context of HSV‑1 infection, as well as to assess its potential as an anti‑HSV‑1 therapeutic agent. The results of the present study demonstrated that JD‑02 exhibits lower cytotoxicity relative to the conventional Hsp90 inhibitor, AT533, and effectively inhibits infection by both standard and ACV‑resistant HSV‑1 strains <i>in vitro</i>. Additionally, JD‑02 markedly suppresses the expression of viral‑associated genes and proteins. The present investigation further revealed that the Raf/MEK/ERK signaling pathway is activated during HSV‑1 infection, and that JD‑02 exerts its antiviral effects through the inhibition of this pathway. Moreover, the in vivo administration of JD‑02 mitigated the symptoms of Herpes simplex encephalitis (HSE), extended the lifespan of mice with HSE, and decreased both the viral gene copy number and the expression of inflammatory factors. In contrast to targeting viral DNA polymerases, Hsp90 inhibitors, which target host proteins, exhibit a significantly lower likelihood of inducing drug resistance. These findings indicate that JD‑02, a novel HSP90 inhibitor, holds promise for development as a therapeutic agent for the treatment of HSV‑1 infection and associated diseases.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"57 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147528505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}