EXPERT OPINION ON THERAPEUTIC TARGETS治疗靶点专家意见
EXPERT OPINION ON THERAPEUTIC TARGETS(英文缩写 EXPERT OPIN THER TAR),ISSN 1472-8222,eISSN 1744-7631,中文译名:治疗靶点专家意见 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.797 | Q1 |
| 2022 | 5.800 | Q1 |
| 2023 | 4.600 | Q1 |
| 2024 | 4.400 | Q1 |
| 2025 | 5.100 | Q1 |
EXPERT OPINION ON THERAPEUTIC TARGETS 最新收录文献
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1. Targeting the LOX-1 scavenger receptor for therapeutics and diagnostics.
1. 靶向LOX-1清道夫受体用于治疗和诊断PMID:日期:2026-10-04Vascular dysfunction underpins major pathologies including cardiovascular disease, stroke, and cancer. Lipid particle (LP) recognition, processing, and metabolism impacts on vascular health and disease. Membrane proteins termed scavenger receptors (SRs) recognize modified LPs to mediate signaling, trafficking, and processing in cells and tissues. We explore the role of the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, OLR1) in pathophysiology including myocardial infarction, stroke, type 2 diabetes, and cancer. Oxidized LDL (oxLDL) activation of LOX-1 promotes cellular responses associated with cell dysfunction, highlighting this molecular target in disease prevention, therapy, and diagnostics. Furthermore, we evaluate emerging therapeutic modalities including monoclonal antibodies, peptides, small molecules, and nucleic‑acid-based agents and consider the translational potential of LOX-1-targeted diagnostics, particularly in point-of-care settings. Multiple lines of evidence indicate that LOX-1 expression and function is low or negligible during normal physiology; however, LOX-1 expression and signaling are elevated under pro-inflammatory conditions. LOX-1 signaling is associated with NF-kB activation, gene expression, cell proliferation, and apoptosis. Blocking LOX-1-linked cellular responses has beneficial outcomes in pathophysiological states. The development of LOX-1-specific therapeutic and diagnostic agents, particularly those suitable for point-of-care use, represents a promising avenue for multi-disease intervention.
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2. {"_":"Structure-guided targeting of aminopeptidase P: exploiting S4' dimer-interface interactions for selective antimalarial drug design.","i":["Plasmodium falciparum"]}
PMID:日期:2026-10-03Malaria remains a major global infectious disease, and resistance to frontline antimalarial therapies continues to drive the search for novel drug targets. aminopeptidase P (PfAPP) is emerging as a promising target because it performs a specialized role in hemoglobin-derived peptide metabolism. This review discusses the biological role of PfAPP within parasite amino acid recycling, its relationship to other malaria metalloaminopeptidases, structural features governing substrate recognition, and recent progress in hydroxamate-based inhibitor development. Particular emphasis is placed on structure-guided discovery of potent PfAPP inhibitors and on the S4' subsite and Tyr617-mediated dimer-interface interaction as the principal currently defined structural determinants of PfAPP inhibitor potency and parasite selectivity. PfAPP has strong target credentials because it combines biological essentiality, unique Xaa-Pro substrate specificity, structural tractability and exploitable divergence from human aminopeptidase P homologues. However, current inhibitors remain limited by poor permeability and modest whole-parasite activity. The most promising future direction is the conversion of potent peptide-like hydroxamates into drug-like compounds that preserve S4' engagement while improving parasite exposure.
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3. Sirtuin signaling as therapeutic targets of immunosenescence.
PMID:日期:2026-09-25Aging is characterized by immunosenescence, encompassing, immune aging and inflammaging. Because immune competence is a critical determinant of lifespan and healthspan, targeting immunosenescence has become a major objective of geroscience. In this context, sirtuins have emerged as compelling therapeutic candidates. This review examines the role of sirtuin signaling in immunosenescence, focusing on its links with nicotinamide adenine dinucleotide (NAD)+ metabolism, oxidative stress, and inflammatory pathways. Pharmacological strategies aimed at enhancing sirtuin activity, including natural and synthetic activators as well as NAD+ precursors, are critically discussed. Sirtuin signaling represents a biologically plausible strategy for targeting immunosenescence, as it integrates metabolic, mitochondrial, epigenetic, and inflammatory pathways involved in the age-related remodeling of innate and adaptive immunity. However, sirtuin modulation remains investigational rather than an established therapeutic approach. Although NAD precursors and sirtuin activators have yielded encouraging preclinical findings, robust evidence of clinically meaningful effects in humans is still lacking. Further progress will require validated biomarkers of immunosenescence, appropriately selected study populations, adequately powered randomized trials incorporating functional and clinically relevant immune endpoints, and long-term safety assessment. At present, mTOR-directed interventions appear closer to clinical translation, whereas NAD- and sirtuin-based approaches remain promising complementary strategies requiring further investigation.
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4. Molecular insights into GLP-1 receptor agonists and emerging metabolic-inflammatory targets in hidradenitis suppurativa.
4. GLP-1受体激动剂及化脓性汗腺炎中新出现的代谢-炎症靶点的分子机制研究PMID:日期:2026-09-24Hidradenitis suppurativa (HS) is increasingly recognized as a systemic immunometabolic disease associated with obesity, insulin resistance, and metabolic syndrome (MetS). A metabolically unhealthy lean phenotype indicates that metabolic dysfunction and chronic low-grade inflammation may occur independently of increased body mass index (BMI) in patients with HS. Reduced effectiveness of biologic therapies in patients with obesity further supports targeting the upstream metabolic drivers of inflammation. This review outlines metabolic-inflammatory pathways proposed to contribute to HS, including insulin/insulin-like growth factor 1 (IGF-1) signaling, mechanistic target of rapamycin complex 1 (mTORC1) overactivation, adipokine dysregulation, and gut-skin interactions. Building on this framework, this review evaluates evidence on glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual incretin agonists, and other metabolic interventions, including metformin is evaluated. GLP-1RAs may serve as adjunctive metabolic therapies for selected patients with HS and obesity or MetS. By promoting weight loss and metabolic improvement, they may reduce systemic inflammation, perioperative risk, and improve responses to weight-based biologics. However, current evidence remains mainly observational and is confounded by concomitant therapies. Randomized controlled trials using well-defined dermatological and metabolic endpoints are needed before routine implementation.
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6. Extracellular vesicles redefine immune modulation through Toll-like receptor networks.
PMID:日期:2026-09-23Extracellular vesicles (EVs) are potent immunomodulators that can promote the transition from pro-inflammatory to regulatory immune responses across diverse pathological conditions. Tissue injury increases the release of damage- and pathogen-associated molecular patterns (DAMPs and PAMPs), which activate Toll-like receptors (TLRs) to rapidly initiate inflammatory and antiviral responses. Here, we propose that TLR signaling serves as a central axis through which EVs exert both pathogenic and therapeutic effects. This review summarizes current evidence on EV crosstalk with surface and endosomal TLRs and discusses how these interactions may drive long-term reprogramming of target cells. We highlight lipid raft signaling as a unifying mechanism linking TLRs and other receptors to signaling hubs controlling pro- and anti-inflammatory responses. Finally, we propose a model in which EVs act as inducers of trained immunity in immunocompetent cells. EVs have emerged as key immunomodulators that transport diverse DAMPs, transmit danger signals to surrounding tissues, and may establish trained immunity, priming cells for subsequent insults. Conversely, therapeutic EVs can target hyperinflammatory cells by modulating aberrant TLR signaling and reprogramming them toward a restorative, pro-resolving phenotype.
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7. Senolytics for Cancer treatment: complexities and opportunities.
PMID:日期:2026-09-23There is currently growing interest in targeting senescent tumor cells as a strategy for improving the efficacy of cancer therapy. Despite the promise of this strategy, a number of limitations have emerged relating to the utility of senescence-eliminating agents, collectively termed senolytics. First, these compounds show different outcomes in aging and tumor cell models. Second, they exhibit variable efficacy in eliminating senescent tumor cells based on tumor background. Third, efficacious agents do not necessarily eliminate the risk of proliferative recovery that could reflect disease recurrence. Fourth, several of the compounds that demonstrate the highest efficacy against senescent tumor cells are associated with established or potential adverse effects that would limit their translation. Here, we provide an overview of the advantages and disadvantages of established senolytics and explore the potential for newly identified agents strictly tested in tumor cell models. Senolytic translation is constrained by TIS heterogeneity generating resistant subpopulations, potential proliferative recovery, senolytic-associated adverse effects, inability to spare beneficial senescent cells, and absence of validated clinical trial designs. Emerging immune-based strategies nanovaccines, nano-antigen-presenting machinery, and CAR-T platforms offer more selective alternatives, but require validated preclinical and clinical testing for further implementation.
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8. In the wisdom of Odin: modular architecture, receptor trafficking and therapeutic implications.
PMID:日期:2026-09-22Odin (ANKS1A) is a multidomain adaptor protein originally identified as a substrate of receptor tyrosine kinases. Over the past two decades, studies have revealed functions that extend beyond canonical growth factor signaling. At the molecular level, Odin participates in receptor signaling and membrane trafficking pathways, while at the cellular and physiological levels it contributes to processes such as ependymal cell development, ciliogenesis, and neurovascular homeostasis. Consistent with these diverse functions, alterations in Odin expression or activity have been linked to an expanding spectrum of human diseases, including cancer, neurodevelopmental disorders, neurodegeneration, ciliopathies, and cardiovascular diseases. In this review, we summarize current knowledge of Odin structure and function, with particular emphasis on how its conserved modular architecture may support its role as a coordinator of receptor trafficking, signaling, and membrane homeostasis. We further discuss emerging evidence linking Odin dysfunction to human diseases and review the limited therapeutic strategies currently available. Collectively, we propose a model in which Odin functions through its conserved multidomain architecture. A deeper understanding of its structural organization and molecular mechanisms may not only reveal fundamental principles of receptor regulation but also establish Odin as a promising, yet largely unexplored, therapeutic target.
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9. Targeting the Orai1 CRAC channel: translating molecular insights into therapeutic progress.
9. 靶向Orai1 CRAC通道：将分子见解转化为治疗进展PMID:日期:2026-09-21The Ca release-activated Ca (CRAC) channel, triggered by the interaction between the Ca sensor STIM1 and Orai1, is the primary mediator of store-operated calcium entry (SOCE). Dysregulation of this process drives numerous human pathologies, particularly immune disorders and cancer hallmarks. Due to its role, Orai1 has emerged as an attractive target for precision therapeutics. This review outlines the pharmacological evolution of CRAC channel modulators, tracing their development from early chemical tools, such as SKF-96365, that exhibits several off-target effects, to more selective second-generation pore blockers, including Synta66, RO2959 or GSK-7975A. Particular attention is paid to third-generation inhibitors, especially CM4620 (zegocractin), evaluating data from recent Phase 2 clinical trials in acute pancreatitis (CARPO), severe COVID-19 pneumonia (CARDEA), and acute kidney injury (KOURAGE). We describe emerging orally bioavailable candidates like CM5480 aimed at chronic cardiopulmonary remodeling. Clinical experience reveals that targeting ubiquitous Ca pathways, such as SOCE, demands specific trial design, transitioning toward biomarker-driven stratification of patient cohorts. Over the coming years, the pharmacological design will diverge into acute intravenous critical care and chronic oral immunomodulation. Ultimately, the exploitation of tissue-specific Orai2 and Orai3 isoform profiles represents the next frontier to enhance therapeutic efficacy across distinct disorders.
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10. The serotonin 1B receptor as a target for the treatment of depression and anxiety.
PMID:日期:2026-09-21Depressive and anxiety disorders impose a substantial public health burden, yet current serotonergic therapies are limited by delayed onset, modest remission rates, and adverse side effects. Here we put forward the serotonin 1B receptor (5-HT1BR) as an important therapeutic target for mood related pathology. We synthesize converging evidence from human and preclinical studies that link 5-HT1BR expression and function to affective phenotypes. Importantly, agonists and the p11 dependent surface trafficking pathway produce antidepressant like effects. Additionally, recent work demonstrates that 5-HT1BR signaling is required for the sustained pro-hedonic and anxiolytic actions of psilocybin. Mechanistically, 5-HT1BR modulates corticolimbic synaptic plasticity and regulates neurotransmitter release from both serotonergic and non-serotonergic terminals, positioning it to reshape dysfunctional neural circuitry. FDA-approved drugs that have 5-HT1BR agonist activity show favorable safety profiles, but there is limited clinical data from brain penetrant selective ligands. We propose prioritized research avenues: PET-based occupancy biomarkers, clinical trials with 5-HT1BR agonists, and exploration of sex and stress dependent effects. Additionally, in the recent drive to study and develop novel psychedelic-related compounds, it is important to consider 5-HT1BR activation. Collectively, preclinical evidence supports 5-HT1BR as a tractable, high-impact target poised to contribute to antidepressant strategies.