MEDICINAL RESEARCH REVIEWS药物研究评论
MEDICINAL RESEARCH REVIEWS(英文缩写 MED RES REV),ISSN 0198-6325,eISSN 1098-1128,中文译名:药物研究评论 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 | 12.388 | Q1 |
| 2022 | 13.300 | Q1 |
| 2023 | 10.900 | Q1 |
| 2024 | 11.600 | Q1 |
| 2025 | 13.600 | Q1 |
MEDICINAL RESEARCH REVIEWS 最新收录文献
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1. The Executioners of Mitochondrial Apoptosis: Structures, Mechanisms, and Therapeutic Advances of BAX, BAK, and BOK.
PMID:日期:2026-10-03The BCL-2 family effector proteins BAX, BAK, and BOK are pivotal regulators of the mitochondrial apoptosis pathway. They act as the ultimate executioners responsible for the irreversible step of mitochondrial outer membrane permeabilization. Their molecular conformations and dynamic changes determine the initiation of mitochondrial apoptosis and are intimately linked to the pharmacological efficacy of apoptotic modulators. This review provides a comprehensive analysis of the intricate structural mechanisms that govern activation, oligomerization, and pore formation of BAX, BAK, and BOK. Furthermore, this review summarizes the crucial sites involved in regulating their activity, as well as the latest advances in pharmacological strategies aimed at directly modulating their activity. These contents offer valuable insights for the development of apoptosis-based therapies and drug targets.
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2. Molecular Glue Degraders in Early Development for Cancer Therapy.
2. 用于癌症治疗的早期开发中的分子胶降解剂PMID:日期:2026-09-07Molecular glue degraders are an emerging class of small molecule allosteric modulators that induce or stabilize protein-protein interactions, enabling targeted degradation of previously intractable proteins. By redirecting E3 ligases to recognize neosubstrates, proteins that are not typically recognized by a specific E3 ubiquitin ligase, they expand the scope of drug discovery beyond traditional paradigms. We review mechanistic principles underlying molecular glue activity, including cooperativity, weak affinity interactions, structural degrons, and higher-order complex formation. We discuss discovery strategies, from serendipitous identification to emerging rational and chemoproteomic approaches, and key E3 ligase systems with relevance to oncology. We highlight clinical and preclinical applications, alongside challenges such as resistance mechanisms, context-dependent activity, and limitations in predicting neosubstrates. Molecular glues are transitioning from serendipitous discoveries to a mechanism-driven therapeutic platform. Progress depends on integrating structural biology, proteomics, and computational modeling to enable rational design and improve predictability. Expanding the repertoire of E3 ligases and understanding context-specific degradation will be critical to fully realize their potential in oncology and beyond.
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3. N-Myristoylation: A Central Hub Integrating Tumor Signaling, Metabolism, and Immunity for Precision Therapy.
PMID:日期:2026-09-07Lipid modifications are critical for membrane anchoring and signal transduction. N-myristoylation, catalyzed by NMT1/2, irreversibly attaches myristic acid to N-terminal glycine residues, enabling stable membrane localization and crosstalk with other post-translational modifications. This review traces NMT research from structural characterization to substrate profiling, highlighting the ordered double-substitution catalytic mechanism and variations in substrate recognition. While prior reviews have covered NMT biochemistry and innate immunity, we emphasize underappreciated roles of N-myristoylation in metabolic vulnerability, immune evasion, and acquired resistance to targeted therapies and immunotherapies. We discuss how exogenous myristic acid from dietary sources fuels oncogenic signaling, and how N-myristoylation regulates key signaling pathways (PI3K/AKT, MAPK, ferroptosis) and targets (Src, AMPK, EZH2) to drive immunosuppressive and pro-tumor phenotypes. Antitumor potential of NMT inhibitors (e.g., B-13, Zelenirstat) and allosteric ABL1 inhibitors (asciminib) is evaluated. Recent methodological advances (including metabolic labeling, click chemistry, spatial proteomics, and computational simulations) are reviewed. However, translational challenges such as biomarker absence, blood-brain barrier limitations, and functional redundancy remain. Addressing these will require combination therapies tailored to specific mutational, metabolic, and immune profiles. In summary, N-myristoylation integrates signaling, metabolism, and immunity, offering a rationale for future precision oncology.
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4. Ferroptosis in Intestinal Diseases: Molecular Mechanisms, Therapeutic Potential, and Future Perspectives.
4. 肠道疾病中的铁下垂：分子机制、治疗潜力和未来前景PMID:日期:2026-08-25Ferroptosis is an iron-driven, regulated form of cell death characterized by the gradual accumulation of lipid peroxides within the cell membrane. Intestinal diseases, including inflammatory bowel disease (IBD), ischemia-reperfusion injury (IRI), and colorectal cancer (CRC), are becoming increasingly prevalent and pose a significant burden on public health. Emerging evidence suggests that ferroptosis plays a context-dependent role in these conditions: inhibiting ferroptosis in normal intestinal epithelial cells can mitigate tissue damage, whereas inducing ferroptosis in malignant cells serves as a strategy to suppress tumor progression and metastasis. This review systematically integrates the latest insights into the molecular mechanisms regulating ferroptosis, the pathophysiology of various intestinal diseases, and translational therapeutic strategies. We highlight the therapeutic potential of targeting ferroptosis using inducers or inhibitors (often in combination with the gut microbiota, chemotherapy, radiotherapy, immunotherapy, and nanodrug delivery systems). Despite these advances, significant challenges remain, including the lack of standardized detection methods, variability across experimental models, drug-specific limitations, and safety concerns. In the future, the development of clinically relevant biomarkers, precise drug delivery platforms, and robust translational frameworks will be critical to realizing the potential of ferroptosis-targeted therapies. By integrating mechanistic, pathological, and therapeutic perspectives, this review provides a comprehensive roadmap for leveraging ferroptosis to manage intestinal diseases.
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5. Developing the Dopamine D3 Receptor (D3R) Antagonist, (R)-VK4-116, as a Non-Opioid Medication for the Treatment of Opioid Use Disorder.
PMID:日期:2026-08-25Opioid use disorder (OUD) remains a major global health challenge, and currently approved treatments (methadone, buprenorphine, and naltrexone) are all opioid receptor-targeting drugs with limitations in access, adherence, stigma, and use in polysubstance use disorders. Because the dopamine D3 receptor (D3R) is enriched in limbic brain regions involved in reward, drug dependence, and impulse control, it has become an attractive target for treating OUD and related substance use disorders. This review first surveys the emerging field of D3R antagonists as non-opioid therapeutics for substance use disorders, including D3R-selective compounds that have advanced into clinical development. We then present VK4-116 as a representative case study of translational progress in this field. Guided by D3R crystal structure-based modeling and medicinal chemistry optimization, VK4-116 was identified as a highly D3R-selective antagonist with favorable brain penetration and in vivo activity. In rodent models, VK4-116 reduced opioid self-administration, drug seeking, withdrawal-induced hyperalgesia, and irritability-like behavior, while enhancing opioid analgesia and reversing cocaine-induced cognitive deficits. The eutomer, (R)-VK4-116, was advanced through preclinical development, including scalable good manufacturing practices-compatible synthesis, formulation optimization to improve oral bioavailability, and investigational new drug-enabling toxicology studies defining toxicity endpoints, the no observed adverse effect level, and a safe clinical starting dose. Together, these findings support clinical evaluation of (R)-VK4-116 and illustrate the therapeutic promise of D3R antagonists for OUD and polysubstance use disorders.
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6. Application of Pyrrolidine in FDA-Approved Drugs.
PMID:日期:2026-08-18The saturated five-membered pyrrolidine ring is a privileged scaffold in medicinal chemistry. There is great interest in the pyrrolidine skeleton due to several key characteristics of this heterocyclic ring: its sp hybridized carbon framework, the contribution of multiple chiral centers, and the inherent planarization of the ring, typically manifested as conformational flexibility or pseudorotation. These characteristics make pyrrolidine-based structures highly attractive in the drug design for various biological targets. The pyrrolidine moiety also enhances drug-like properties such as metabolic stability, water solubility, and modulation of basicity, and can interact favorably with a wide range of biological targets through specific stereochemical interactions. This review surveys the synthesis and clinical applications of FDA-approved pyrrolidine-containing drugs since 2014, with the aim of informing the rational design of next-generation pyrrolidine-based therapeutics.
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7. Unraveling the Intricacies of G-Protein-Coupled Receptor Signaling in Cardiovascular Diseases: Novel Perspectives From Regulation to Therapeutic Targeting.
PMID:日期:2026-08-17G-protein-coupled receptors (GPCRs) represent a compelling intersection of structural biology, systems pharmacology, and clinical medicine. They function as essential molecular regulators of cardiovascular physiology, governing processes from the initiation of cardiac rhythm in the sinoatrial node to the regulation of vascular tone. Their widespread expression in cardiac and vascular tissues, combined with their ability to integrate diverse extracellular signals, positions GPCRs as key regulators of heart rate, contractility, vascular tone, inflammation, and metabolic homeostasis. Recent advances in GPCR structural biology, coupled with mechanistic insights into G-protein- and β-arrestin-mediated signaling mechanisms, underscore their central role in both cardiovascular health and disease. Notably, dysregulation of GPCR signaling has emerged as a unifying mechanism across major cardiovascular diseases (CVDs), contributing to pathological remodeling, impaired contractile function, and maladaptive vascular responses. This review uniquely integrates GPCR structural biology, signaling dynamics, and mechanosensitive and biased signaling mechanisms within the cardiovascular system. We discuss the contributions of class A, class B, and other GPCR families to cardiovascular physiology and pathology emphasizing their relevance to the development of targeted interventions for hypertension, heart failure, arrhythmias, atherosclerosis, and related CVDs. Together, these insights establish a contemporary framework for advancing precision GPCR-directed therapies in CVDs. By framing these developments within a mechanistic and translational context, the review offers a timely and clinically significant resource for both basic researchers and clinicians.
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8. Boronic Acid Inhibitors of β-Lactamases: A Promising Strategy Against Antimicrobial Resistance.
8. β-内酰胺酶的硼酸抑制剂：对抗 antimicrobial resistance 的一种有前景的策略PMID:日期:2026-08-14The rise of antimicrobial resistance (AMR) poses a critical threat to global health, mostly due to the proliferation of β-lactamases, a class of enzymes responsible for the inactivation of β-lactam antibiotics. Among the most promising strategies to restore β-lactam efficacy is the use of β-lactamase inhibitors (BLIs), with boronic acid derivatives emerging as a pivotal and chemically versatile class. These compounds act as transition-state analogs, forming reversible covalent bonds with the catalytic serine of serine β-lactamases (SBLs), effectively mimicking the tetrahedral intermediate of β-lactam hydrolysis. Their electron-deficient boron atom, combined with a tunable scaffold, allows fine modulation of potency, selectivity, and pharmacokinetic properties. This review traces the evolution of boronic acid-based BLIs from early phenylboronic acids to next-generation acyclic and cyclic derivatives, highlighting key structure-activity relationships, binding mechanisms, and microbiological profiles. Clinically approved agents such as vaborbactam, as well as investigational compounds including taniborbactam, xeruborbactam, and benzoxaboroles, are discussed in the context of their therapeutic relevance and spectrum of activity. Particular attention is given to their ability to inhibit class A and C enzymes, with ongoing efforts aimed at extending coverage to class D and metallo-β-lactamases. Additionally, the review explores innovative approaches such as kinetic target-guided synthesis and fragment-based design to expand the chemical space of boronic acid pharmacophores. Together, these advances underscore the potential of boronic acid-based BLIs as powerful tools in overcoming β-lactamase-mediated resistance and developing next-generation antimicrobial therapies.
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9. Artificial Intelligence-Driven Natural Product Drug Discovery: From Computational Genome Mining to Clinical Translation.
9. 人工智能驱动的天然产物药物发现：从计算基因组挖掘到临床转化PMID:日期:2026-08-07Natural products (NPs) have historically yielded numerous therapeutic agents, yet their integration into modern drug discovery has been constrained by chemical complexity, low abundance, laborious dereplication, and limited target annotation. Convergence of multi-omics technologies with high-resolution structural and biological data has created unprecedented opportunities for artificial intelligence (AI) to accelerate NP-based therapeutics development. This review provides an operational, end-to-end workflow that explicitly connects computational predictions to medicinal chemistry decision points, addressing a critical gap between computational prediction and clinical translation. We trace the complete discovery pipeline: computational mining of biosynthetic gene clusters (BGCs) and metabolomes, deep learning (DL)-assisted structural elucidation and dereplication, network-based target identification using protein-ligand prediction, and generative molecular design inspired by NP scaffolds (including large language models, diffusion models, and genetic algorithms). Critical evaluation of current limitations (data scarcity, lack of standardized ontologies, model interpretability) is complemented by discussion of emergent strategies (foundation models trained on multi-modal data, graph neural networks, autonomous closed-loop laboratories). Representative case studies, including the synthetic AI-designed clinical benchmark rentosertib, illustrate the current evidence spectrum from discovery-level validation to early clinical benchmarking, while also highlighting that most AI-enabled NP discovery workflows remain at the preclinical or proof-of-concept stage, with limited quantitative evidence of improved clinical productivity. We conclude with an Outlook proposing feasible developments for 2025-2030: self-driving laboratories with reported acceleration in specific experimental contexts, foundation models enabling hypothesis-free chemical space exploration, and sustainability-aware AI frameworks embedding biodiversity impact assessments. This operational focus fills a critical gap between algorithmic capability and clinically actionable NP-derived leads. Importantly, while AI has demonstrably accelerated several early discovery steps, quantitative comparisons with classical NP workflows remain limited, and most reported advances are supported by preclinical or proof-of-concept studies rather than systematic evidence of improved time-to-lead, cost reduction, or clinical success rates.
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10. Advancing Therapies for Mycobacterial Diseases: From Small Molecules to Host-Directed Strategies.
10. 推进分枝杆菌疾病治疗：从小分子到宿主导向策略PMID:日期:2026-08-04The global burden of multidrug-resistant tuberculosis (MDR-TB) and the rising incidence of nontuberculous mycobacterial (NTM) infections highlight the urgent need for innovative therapeutic strategies. Current treatments are prolonged, toxic, and increasingly compromised by resistance and limited diagnostic capacity. This review focuses on emerging therapeutic strategies against Mycobacterium tuberculosis (Mtb) and highlights evidence relevant to NTM whenever available. Specifically, it explores direct anti-mycobacterial small molecules, including the optimization of drug classes, such as hydrazide-hydrazones, isoniazid derivatives, nitrofurans, multicomponent forms, and metal complexes, as well as emerging chemical entities in early-stage development. These compounds target essential bacterial enzymes such as decaprenylphosphoryl-β-d-ribose oxidase (DprE1), enoyl acyl carrier protein reductase (InhA), and deoxyribonucleic acid (DNA) gyrase inhibitors, offering promising avenues for overcoming resistance. The review also examines natural products and phytochemicals, including siderophore inhibitors, plant-derived compounds, and essential oils. Non-classical strategies such as antimicrobial peptides (AMPs) and phage therapy are also discussed. Finally, we discuss the expanding field of host-directed therapies (HDTs), which aim to modulate the host immune response to enhance mycobacterial clearance and reduce tissue damage. Ultimately, advancing mycobacterial treatment will require integrated, mechanism-based regimens that combine new compounds with HDTs and improved delivery systems. Although therapeutic innovation for NTM has lagged, adapting promising TB-focused compounds and implementing NTM-specific screening and validation frameworks are essential. Collaborative efforts across academia, industry, and the public health sector will be key to translating these advances into shorter, safer, and more effective therapies that address the complexity of mycobacterial disease and the rise of antimicrobial resistance.