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Trends in pharmacological sciences最新文献

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ROCK2 inhibitor targets vascular niche angiocrine signaling in liver fibrosis. ROCK2抑制剂在肝纤维化中靶向血管壁龛血管分泌信号。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-05-13 DOI: 10.1016/j.tips.2026.04.006
Pingxin Sun, Chunyan Wang, Wenlin Li
{"title":"ROCK2 inhibitor targets vascular niche angiocrine signaling in liver fibrosis.","authors":"Pingxin Sun, Chunyan Wang, Wenlin Li","doi":"10.1016/j.tips.2026.04.006","DOIUrl":"10.1016/j.tips.2026.04.006","url":null,"abstract":"<p><p>Hu et al. identifies that Rho-associated coiled-coil containing kinase 2 (ROCK2) upregulation in sinusoidal endothelial and perivascular cells drives liver fibrosis via pro-fibrotic angiocrine signaling. The selective ROCK2 inhibitor TDI01 reverses fibrosis preclinically and demonstrates safety and target engagement in patients, highlighting vascular niche targeting as a therapeutic strategy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"587-589"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147933629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of RNA-targeting small-molecule therapeutics. rna靶向小分子疗法的发展。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-05-22 DOI: 10.1016/j.tips.2026.04.011
Walter J Zahurancik, Vaishnavi Sidharthan, Roopa Biswas, Venkat Gopalan
{"title":"Development of RNA-targeting small-molecule therapeutics.","authors":"Walter J Zahurancik, Vaishnavi Sidharthan, Roopa Biswas, Venkat Gopalan","doi":"10.1016/j.tips.2026.04.011","DOIUrl":"10.1016/j.tips.2026.04.011","url":null,"abstract":"<p><p>Development of robust RNA-targeting therapeutics to treat diseases requires an understanding of the structural plasticity of ligand-binding pockets in RNAs and the complexity of RNA interactions in vivo. Refocusing efforts toward new RNA-targeted compound libraries and large-scale RNA structural studies will help design successful screens and accelerate RNA-centered drug discovery.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"598-602"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanistic insights into nitazenes at the μ-opioid receptor. nitazene在μ-阿片受体中的作用机制。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-05-14 DOI: 10.1016/j.tips.2026.04.009
Lijie Xia, Meng Jin, Lin Lu
{"title":"Mechanistic insights into nitazenes at the μ-opioid receptor.","authors":"Lijie Xia, Meng Jin, Lin Lu","doi":"10.1016/j.tips.2026.04.009","DOIUrl":"10.1016/j.tips.2026.04.009","url":null,"abstract":"<p><p>Nitazenes, developed as analgesic candidates in the 1950s, were never approved because of fatal side effects. In this forum article, we integrate current mechanistic insights into nitazenes' functionality and discuss their activity at the μ-opioid receptor and the implications of their use in vivo.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"594-597"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147943009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dendrimers in cancer therapy: emerging clinical design strategies. 树突状分子在癌症治疗中的应用：新兴的临床设计策略。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-05-07 DOI: 10.1016/j.tips.2026.04.005
Jinyu Li, Hang Fai Kwok
{"title":"Dendrimers in cancer therapy: emerging clinical design strategies.","authors":"Jinyu Li, Hang Fai Kwok","doi":"10.1016/j.tips.2026.04.005","DOIUrl":"10.1016/j.tips.2026.04.005","url":null,"abstract":"<p><p>Dendrimers are highly branched synthetic polymers whose well-defined architecture enables high drug loading and payload protection. However, their clinical translation in oncology has been hindered by systemic toxicity, inefficient tumor targeting, and premature drug release. To overcome these barriers, recent advances have converged on three integrated design strategies: surface modification and biodegradable backbones to ensure safety; physicochemical tuning and ligand conjugation to enhance tumor targeting; and stimuli-responsive linkers to enable controlled drug release. The clinical progress of DEP-SN38 (DEP, dendrimer-nanoparticle delivery platform) (Starpharma Holdings), a dendrimer-drug conjugate, exemplifies the successful translation of these principles. In this review, we discuss these strategies and analyze how their interplay addresses key clinical challenges, with a focus on their relevance to ongoing and future clinical development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"680-693"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting competitive Fe-S regulation to treat Friedreich's ataxia. 针对竞争性Fe-S调控治疗弗里德赖希共济失调。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-05-18 DOI: 10.1016/j.tips.2026.04.010
Juliane C Campos, Julio C B Ferreira
{"title":"Targeting competitive Fe-S regulation to treat Friedreich's ataxia.","authors":"Juliane C Campos, Julio C B Ferreira","doi":"10.1016/j.tips.2026.04.010","DOIUrl":"10.1016/j.tips.2026.04.010","url":null,"abstract":"<p><p>Recent discoveries reveal that frataxin (FXN) and ferredoxin 2 (FDX2) competitively regulate mitochondrial iron-sulfur (Fe-S) cluster biosynthesis through their binding to the cysteine desulfurase NFS1 and the iron-sulfur cluster scaffold protein ISCU2 complex. Here, we discuss the potential of rationally designed peptide inhibitors targeting the FDX2-NFS1 interaction as a strategy to mitigate FXN deficiency and restore Fe-S cluster biosynthesis.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"590-593"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting peptide-HLA complexes for precision immunotherapy. 靶向肽- hla复合物用于精确免疫治疗。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-01-12 DOI: 10.1016/j.tips.2025.11.007
Jie Bi, Lingxiao Jiang, Jiaqi Zhao, Xinlei Zhuang, Liqiang Pan
{"title":"Targeting peptide-HLA complexes for precision immunotherapy.","authors":"Jie Bi, Lingxiao Jiang, Jiaqi Zhao, Xinlei Zhuang, Liqiang Pan","doi":"10.1016/j.tips.2025.11.007","DOIUrl":"10.1016/j.tips.2025.11.007","url":null,"abstract":"<p><p>Precision immunotherapy leverages the immune system to selectively eliminate abnormal cells while sparing healthy cells. Targeting specific peptide-human leukocyte antigen (pHLA) complexes, derived from cancer, autoimmune, and infectious disease, enables precise intervention, because these antigens are minimally expressed in normal tissues. However, designing binders with high specificity and low cross-reactivity remains challenging. Inspired by natural T cell receptor (TCR) recognition of pHLA complexes, synthetic approaches, including TCR-mimic antibodies (TCRm) and de novo pHLA binders, are emerging, adaptable into T cell engagers and adoptive therapies with promising specificity and efficacy. Moreover, advances in artificial intelligence (AI)-driven methods, immunopeptidomics, and computational protein design are accelerating the discovery and pan-allelic development of highly specific pHLA therapeutics. In this review, we discuss current approaches, mechanisms, preclinical and clinical data, and cutting-edge technologies shaping the future of pHLA-targeted immunotherapies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"603-621"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Click chemistry charts covalent drug landscapes in vivo. 点击体内共价药物的化学图。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-04-11 DOI: 10.1016/j.tips.2026.03.005
Wenhui Wang, Yang Liu, Gaofei Wei
{"title":"Click chemistry charts covalent drug landscapes in vivo.","authors":"Wenhui Wang, Yang Liu, Gaofei Wei","doi":"10.1016/j.tips.2026.03.005","DOIUrl":"10.1016/j.tips.2026.03.005","url":null,"abstract":"<p><p>Covalent drugs display rich in vivo reactivity landscapes that remain largely unmapped. A recent Cell study by Pang et al. introduces vCATCH (volumetric clearing-assisted tissue click chemistry), a chemistry-driven platform combining clickable probes, bioorthogonal ligation, and whole-body imaging to chart covalent drug-target interactions across intact organisms.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"584-586"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacological strategies targeting chaperone-mediated autophagy. 针对伴侣介导的自噬的药理学策略。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-04-20 DOI: 10.1016/j.tips.2026.03.008
Eva Berenger, Alice Maestri, Daniel R Vaz, Elena Kochetkova, Erik Norberg, Vitaliy O Kaminskyy, S Joseph Endicott, Helin Vakifahmetoglu-Norberg
{"title":"Pharmacological strategies targeting chaperone-mediated autophagy.","authors":"Eva Berenger, Alice Maestri, Daniel R Vaz, Elena Kochetkova, Erik Norberg, Vitaliy O Kaminskyy, S Joseph Endicott, Helin Vakifahmetoglu-Norberg","doi":"10.1016/j.tips.2026.03.008","DOIUrl":"10.1016/j.tips.2026.03.008","url":null,"abstract":"<p><p>Chaperone-mediated autophagy (CMA) is a selective lysosomal protein degradation pathway that regulates proteostasis, metabolism, and stress adaptation. Genetic- and disease-model studies show that altered CMA activity contributes to diverse human disorders, including neurodegenerative, metabolic, inflammatory, and malignant diseases. However, pharmacological targeting has remained challenging due to a limited understanding of its regulatory architecture and a lack of criteria to distinguish pathway-selective from indirect modulation. Recent advances in mapping CMA regulatory checkpoints and the in vivo validation of CMA-biased compounds have revealed discrete, mechanistically defined control nodes that render CMA pharmacologically tractable. In this review, we synthesize these advances and introduce a mechanistic classification of CMA-modulating compounds by level of action, distinguishing physiological inducers, permissive potentiators, and proximal activators to clarify pathway selectivity and guide translational drug discovery.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"622-637"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zoliflodacin: an oral, first-in-class antibacterial agent for drug-resistant gonorrhea. 唑氟哌啶：一种用于耐药淋病的口服一流抗菌剂。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-05-07 DOI: 10.1016/j.tips.2026.04.007
Katherine L Lev, Sriram Chandrasekaran
{"title":"Zoliflodacin: an oral, first-in-class antibacterial agent for drug-resistant gonorrhea.","authors":"Katherine L Lev, Sriram Chandrasekaran","doi":"10.1016/j.tips.2026.04.007","DOIUrl":"10.1016/j.tips.2026.04.007","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"706-707"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent advances in CDC42 subfamily inhibition and therapeutic potential. CDC42亚家族抑制及其治疗潜力的最新进展。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2026-06-01 Epub Date: 2026-05-22 DOI: 10.1016/j.tips.2026.04.004
Maria Antonietta La Serra, Alka Yadav, Anand K Ganesan, Marco De Vivo
{"title":"Recent advances in CDC42 subfamily inhibition and therapeutic potential.","authors":"Maria Antonietta La Serra, Alka Yadav, Anand K Ganesan, Marco De Vivo","doi":"10.1016/j.tips.2026.04.004","DOIUrl":"10.1016/j.tips.2026.04.004","url":null,"abstract":"<p><p>CDC42 subfamily members of the RHOGTPases exist in either an active or inactive state, each with a distinct but highly flexible structure, making them challenging to target. Abnormal CDC42 activity is linked to various conditions, including cancer, neurological and ophthalmological disorders, skin diseases, and vascular conditions. This has driven increasing interest in developing CDC42 inhibitors, which have recently produced lead compounds demonstrating disease-modifying effects in vivo. In this review, we provide an overview of the physiological functions of CDC42 subfamily members and their emerging roles in disease. We also examine the latest advances in leveraging CDC42's structural features for selective inhibition, analyzing the mode of action and chemical structures of current inhibitors. These insights aim to inform the design of improved molecules with broad therapeutic potential.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"655-679"},"PeriodicalIF":19.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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