Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献_第3页

[Discovery of Streptospherins, Novel Cancer Stem Cell Inhibitors]. [发现链状球蛋白，新型癌症干细胞抑制剂]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.26-00130

Hiroaki Ikeda

{"title":"[Discovery of Streptospherins, Novel Cancer Stem Cell Inhibitors].","authors":"Hiroaki Ikeda","doi":"10.1248/yakushi.26-00130","DOIUrl":"https://doi.org/10.1248/yakushi.26-00130","url":null,"abstract":"Targeting cancer stem cells (CSCs) is a promising strategy for preventing cancer progression and recurrence because of their high malignancy. To identify candidate CSC inhibitors, we established a new screening strategy using colorectal CSC spheres in a three-dimensional culture system. The obtained CSC spheres exhibited elevated expression of stemness markers and resistance to conventional anticancer agents. Using this system, we identified streptospherins A-F (1-6), isolated from Streptomyces sp. KUSC-240, as novel inhibitors of CSC sphere formation. Their planar structures were elucidated by high resolution electrospray ionization mass spectrometry (ESI-MS) and NMR analyses. The absolute configurations of 3-5 were proposed using spectroscopic analyses [J-based configuration (JBCA) analysis and ECD spectral analysis] together with chemical derivatization methods (modified Mosher's method and acetonide formation). A plausible biosynthetic pathway for compounds 3-5 was proposed based on the whole genome sequence analysis of the producing strain. Compounds 1-6 suppressed both CSC sphere formation and CSC proliferation, indicating the potential of streptospherins as promising seed compounds for CSC-targeted cancer chemotherapy.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 10","pages":"837-841"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

[Characterization of Genetic Polymorphisms Related to 5-FU Metabolizing Enzymes in Japanese Populations]. [日本人群5-FU代谢酶相关遗传多态性表征]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00124

Eiji Hishinuma

{"title":"[Characterization of Genetic Polymorphisms Related to 5-FU Metabolizing Enzymes in Japanese Populations].","authors":"Eiji Hishinuma","doi":"10.1248/yakushi.25-00124","DOIUrl":"10.1248/yakushi.25-00124","url":null,"abstract":"Fluoropyrimidine anticancer agents, exemplified by 5-fluorouracil (5-FU), induce severe adverse effects-such as myelosuppression, emesis, diarrhea, and hand-foot syndrome-in approximately 10-30% of patients. As such toxicities can result in delays or discontinuation of therapy, accurate prediction of drug response prior to treatment initiation is of critical importance. The metabolic degradation of 5-FU is primarily mediated by the drug-metabolizing enzymes dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHPase). These enzymes are encoded by the DPYD and DPYS genes, respectively; polymorphisms in these genes that reduce or abolish enzymatic activity lead to elevated systemic concentrations of 5-FU, thereby increasing the risk of severe toxicity. In Caucasian populations, four DPYD polymorphisms have been identified as predictive markers of adverse drug reactions. However, these variants are rarely observed in Japanese individuals, and reliable pharmacogenomic biomarkers remain largely unreported in this population. To address this gap, we conducted a comprehensive in vitro functional analysis of DPD and DHPase activity of DPYD and DPYS variants identified through large-scale whole-genome sequencing databases. This review summarizes our findings and elucidates the underlying mechanisms affecting the function of 5-FU-metabolizing enzymes, as revealed by our prior research.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 1","pages":"1-6"},"PeriodicalIF":0.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

[Realization of Near-future Factories Using Linear Transportation Technology]. [利用线性运输技术实现近未来工厂]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.24-00210-F

Tatsuyuki Iwasaki, Tetsumi Irie, Masahiko Kikuchi

引用次数: 0

[Inflammasome Activation and Idiosyncratic Drug-induced Liver Injury: Fusion Study of Basic and Real-world Data]. [炎性体激活和特异性药物性肝损伤：基础数据和现实数据的融合研究]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00145-2

Ryuji Kato

{"title":"[Inflammasome Activation and Idiosyncratic Drug-induced Liver Injury: Fusion Study of Basic and Real-world Data].","authors":"Ryuji Kato","doi":"10.1248/yakushi.25-00145-2","DOIUrl":"10.1248/yakushi.25-00145-2","url":null,"abstract":"Idiosyncratic drug-induced liver injury (IDILI) is particularly problematic due to its severity and unpredictability. Various pathogenic mechanisms have been proposed for IDILI; however, these mechanisms have yet to be comprehensively elucidated. Although the hapten hypothesis has long been posited as a possible pathogenic mechanism, it is believed that other mechanisms may also elicit a strong immune response. We hypothesized that reactive metabolites generated by drug metabolism cause cellular stress and release damage-associated molecular patterns (DAMPs) that may activate antigen-presenting cells (APCs). We have shown that the metabolites of drugs such as acetaminophen, flutamide, and bicartamide activate the inflammasome response in APCs. Moreover, we confirmed that these reactions are suppressed by steroids. Meanwhile, we are also investigating drugs that are suspected to have an immune-mediated mechanism of action based on basic studies using real-world data. If the pathogenic mechanism of IDILI is indeed immune-mediated, it may be suppressed by steroid administration or activated by the concomitant use of immune checkpoint inhibitors. Additionally, we are analyzing the relative risk rates of these drugs in combination. In this review, we present the findings of our previous studies on the pathogenesis of IDILI, including those on reactive metabolites and immune activation. We also present the results of the real-world data analysis which validated the pathogenic mechanism of IDILI that was previously elucidated through basic research, showcasing our efforts to integrate basic and clinical research.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 2","pages":"111-114"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 a Liver Fibrosis Treatment Targeting Inhibition of Hepatic Stellate Cell Activation]. [靶向抑制肝星状细胞活化的肝纤维化治疗进展]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00126

Momoka Yamaguchi

{"title":"[Development of a Liver Fibrosis Treatment Targeting Inhibition of Hepatic Stellate Cell Activation].","authors":"Momoka Yamaguchi","doi":"10.1248/yakushi.25-00126","DOIUrl":"10.1248/yakushi.25-00126","url":null,"abstract":"Chronic liver disease causes approximately 2 million deaths annually worldwide, accounting for nearly 4% of global mortality. Liver fibrosis is a central pathological feature driving the progression of chronic liver disease (CLD), irrespective of the underlying etiology-be it hepatitis viruses, alcohol consumption, or the increasingly prevalent metabolic dysfunction-associated steatosis. Liver fibrosis arises from a dysregulated wound-healing response following sustained liver injury and inflammation, leading to excessive extracellular matrix deposition that intersects normal liver architecture and function. Despite the significance of fibrosis in CLD progression, effective antifibrotic therapies have not been deduced. A limited subset of metabolic dysfunction-associated steatotic liver disease (MASLD) patients progresses to metabolic dysfunction-associated steatohepatitis (MASH) characterized by inflammation and fibrosis, which indicates that this progression involves specific triggering mechanisms or factors. Hepatic stellate cells (HSCs), located in the space of Disse as quiescent vitamin A-storing cells, are the key mediators of fibrosis. The activation and transdifferentiation of HSCs into myofibroblast-like cells following liver injury results in markedly increased collagen production. Our recent research has indicated that altered adenosine metabolism in hepatocytes leads to increased extracellular adenosine, which in turn drives the activation of HSCs, promoting the progression from MASLD to MASH. The regulatory mechanisms involving prostaglandin E2 and adenosine signaling in the activation of HSCs are complex and have not been fully elucidated. Further detailed investigations that would uncover the complete pathways controlling the activation of HSCs and enable the development of novel therapeutic strategies targeting liver fibrosis in CLD are warranted.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 2","pages":"91-95"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

[Challenging the Elucidation of Anti-inflammatory Mechanisms Using Chemical Probes of Resolvins]. [利用Resolvins的化学探针对抗炎机制的阐明提出挑战]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00130

Hayato Fukuda

{"title":"[Challenging the Elucidation of Anti-inflammatory Mechanisms Using Chemical Probes of Resolvins].","authors":"Hayato Fukuda","doi":"10.1248/yakushi.25-00130","DOIUrl":"10.1248/yakushi.25-00130","url":null,"abstract":"Resolvins are endogenous polyunsaturated fatty acids that show strong anti-inflammatory activity and are therefore expected to be promising new anti-inflammatory drug candidates. However, resolvins have many problems, including instability. This article reviews efforts to improve the stability of resolvin E2 (RvE2) and develop chemical probes to elucidate its anti-inflammatory mechanism. First, to improve the oxidative stability of RvE2, α- and β-CP-RvE2 were designed and synthesized by introducing cyclopropanes (CP) to C11-C12 of RvE2, and the oxidative stability of RvE2 was significantly improved. Next, 5-, 18-, and 20-AP-β-CP-RvE2 were designed and synthesized by introducing azidopropyl (AP) groups to C5, C18, and C20 of β-CP-RvE2 so as to determine the position of introduction of functional groups. The anti-inflammatory activity and phagocytosis of macrophages were evaluated, and it was revealed that 5-AP-β-CP-RvE2 has the same activity as RvE2 and β-CP-RvE2. In addition, to simplify the structure of RvE2, o-, m-, and p-BZ-RvE2 were designed and synthesized by introducing a benzene (BZ) ring into C9-C14 of RvE2. It was found that the metabolic stability of o-BZ-RvE2 was improved compared with RvE2, and the anti-inflammatory activity of o-BZ-RvE2 was equal to or greater than that of RvE2.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 2","pages":"97-104"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

[Current Status and Challenges in the Development of Extracellular Vesicle-based Therapeutic Systems]. [细胞外囊泡治疗系统发展的现状与挑战]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00171-F

Makiya Nishikawa, Yuki Takahashi

引用次数: 0

[Advances in Targeted Protein Degradation Technology]. [靶向蛋白质降解技术进展]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00183-F

Yukihiro Itoh, Fumihiro Ishikawa

引用次数: 0

[Expansion of Targeted Protein Degradation for Targeting Aggregate-prone Proteins and Mitochondrial Proteins]. [扩展靶向蛋白降解靶向聚集倾向蛋白和线粒体蛋白]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00183-2

Shusuke Tomoshige

{"title":"[Expansion of Targeted Protein Degradation for Targeting Aggregate-prone Proteins and Mitochondrial Proteins].","authors":"Shusuke Tomoshige","doi":"10.1248/yakushi.25-00183-2","DOIUrl":"https://doi.org/10.1248/yakushi.25-00183-2","url":null,"abstract":"Targeted protein degradation (TPD), a technology that induces the degradation of a protein of interest (POI) by a chemical degrader, is a major trend in drug discovery research. Proteolysis targeting chimeras (PROTACs) are representative degraders that induce the ubiquitination of a POI, leading to its proteasomal degradation. Following the report of PROTAC efficacy in animals approximately a decade ago, TPD research continues to flourish. Unlike the occupancy-driven mechanism of traditional inhibitors, TPD employs an event-driven mechanism. Consequently, TPD is a highly anticipated technology capable of addressing therapeutic targets previously considered \"undruggable.\" Against this backdrop, our group is actively pursuing research focused on the targeted degradation of undruggable proteins. This symposium review summarizes our studies. It focuses on two distinct areas: the targeted degradation of aggregation-prone proteins for the development of neurodegenerative disorder treatments, and the targeted degradation of mitochondrial matrix-localized proteins for mitochondria-related diseases.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 7","pages":"625-630"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

[Effect of Application Device Design on Scalp Delivery of Topical Minoxidil Formulations]. 应用装置设计对局部米诺地尔制剂头皮给药的影响

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.26-00007

Ayano Kojima, Hiroaki Todo, Yutaka Inoue, Syuuhei Komatsu

{"title":"[Effect of Application Device Design on Scalp Delivery of Topical Minoxidil Formulations].","authors":"Ayano Kojima, Hiroaki Todo, Yutaka Inoue, Syuuhei Komatsu","doi":"10.1248/yakushi.26-00007","DOIUrl":"https://doi.org/10.1248/yakushi.26-00007","url":null,"abstract":"Equivalence of OTC formulations is generally assessed based on pharmaceutical attributes such as active ingredient content, dissolution behavior, and stability. However, for topical liquid formulations that are directly applied to the skin or scalp, the container design and usability may also influence the applied dose and the amount that reaches the target site. Appropriate design of containers or applicator devices is therefore essential for ensuring the effectiveness and safety of OTC topical products. In this study, we investigated the effects of container-tip geometry and hair density on scalp delivery of minoxidil (MXD) using four marketed MXD topical formulations. A scalp model was prepared by covering filter paper with human hair, and we evaluated: (1) the amount of MXD dispensed per actuation from each container, (2) the amount of MXD that reached beneath the hair layer, and (3) the in vitro skin permeation using porcine ear skin. Increased hair density reduced MXD delivery to the scalp for all formulations, especially for containers with larger tip ends. These findings suggest that ensuring the efficacy and reproducibility of MXD-containing OTC topical formulations requires not only optimizing drug permeability and formulation characteristics, but also considering hair density and container-tip geometry in designing appropriate usage conditions.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 7","pages":"669-674"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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