Pharmaceutical Fronts最新文献

Recent Advances in Mitochondrial Pyruvate Carrier Inhibitors 线粒体丙酮酸载体抑制剂的最新进展

Pharmaceutical Fronts Pub Date : 2024-07-15 DOI: 10.1055/s-0044-1788072

Yilei Huang, Han Zhang, Xinyan Peng, Qingwei Zhang

引用次数: 0

Discovery of a Novel Benzimidazole Necroptosis Inhibitor from an In-House Compound Library 从内部化合物库中发现新型苯并咪唑坏死抑制剂

Pharmaceutical Fronts Pub Date : 2024-07-15 DOI: 10.1055/s-0044-1788077

Yu Zou, Yue Chai, Hong-Li Shao, Shuyu Wang, Ruilin Hou, Runhui Liu, Linjing Zhao, Chunlin Zhuang

{"title":"Discovery of a Novel Benzimidazole Necroptosis Inhibitor from an In-House Compound Library","authors":"Yu Zou, Yue Chai, Hong-Li Shao, Shuyu Wang, Ruilin Hou, Runhui Liu, Linjing Zhao, Chunlin Zhuang","doi":"10.1055/s-0044-1788077","DOIUrl":"https://doi.org/10.1055/s-0044-1788077","url":null,"abstract":"Necroptosis, a caspase-independent regulated cell death, is primarily mediated by the serine/threonine kinases RIPK1 and RIPK3, and the mixed lineage kinase domain-like protein (MLKL). Targeting necroptosis is a validated therapeutic strategy for various diseases. We screened compound 1, a novel benzimidazole-based necroptosis inhibitor, from our in-house compound library. We assessed its inhibitory roles and mechanisms in blocking HT-29 cell necroptosis. HT-29 cells were treated with pan caspase inhibitor Z-VAD-FMK + Smac mimetic (TSZ), or Z-VAD-FMK + cycloheximide (TCZ), then with tumor necrosis factor α (TNFα) to induce necroptosis in vitro. Prior to stimulation, cells were exposed to compound 1. GSK'843 served as a control drug. HT-29 cells were treated with TNFα + Smac mimetic (TS) or TNFα + cycloheximide (TC) to induce apoptosis in vitro. Cell viability, cell death, and necroptotic cells were evaluated by luminescence-based CellTiter-Lumi assay or flow cytometry. Western blots, immunoprecipitation, and KINOMEscan technology were used to assess RIPK1, RIPK3, and MLKL's involvement in compound 1's mechanisms. Compound 1's roles in mouse TNFα induced systemic inflammatory response syndrome (SIRS) in mice were also investigated by assessing body temperature, mouse survival rate, and interleukin (IL)-β and IL-6 levels in respective tissues. We found that necroptosis triggered by TSZ or TCZ was effectively mitigated by compound 1, showing a dose-responsive inhibition, and it could protect mice from TNF-induced SIRS. The mechanism study showed that compound 1 could interact with RIPK1, inhibiting RIPK1 phosphorylation activation to block necrosome formation in necroptotic cells. In summary, compound 1 is a promising lead compound for developing treatments targeting diseases associated with necroptosis.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"109 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141647403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Research Strategies for Precise Manipulation of Micro/Nanoparticle Drug Delivery Systems Using Microfluidic Technology: A Review 利用微流体技术精确操纵微/纳米粒子给药系统的研究策略：综述

Pharmaceutical Fronts Pub Date : 2024-05-23 DOI: 10.1055/s-0044-1786180

Jie Liu, Qinghui Fu, Qin Li, Yani Yang, Yue Zhang, Kaili Yang, Guohao Sun, Jiayu Luo, Weigen Lu, Jun He

{"title":"Research Strategies for Precise Manipulation of Micro/Nanoparticle Drug Delivery Systems Using Microfluidic Technology: A Review","authors":"Jie Liu, Qinghui Fu, Qin Li, Yani Yang, Yue Zhang, Kaili Yang, Guohao Sun, Jiayu Luo, Weigen Lu, Jun He","doi":"10.1055/s-0044-1786180","DOIUrl":"https://doi.org/10.1055/s-0044-1786180","url":null,"abstract":"Microfluidic technology facilitates precise control over fluid mixing and interactions between the components, including self-assembly and precipitation. It offers new options for accurately manufacturing particles and holds significant potential in advancing micro/nanoparticle drug delivery systems (DDSs). Various microchannel/microfluidic chips have been explored to construct micro/nanoparticle DDSs. The precise manipulation of particle size, morphology, structure, stiffness, surface characteristics, and elasticity through microfluidic technology relies on specific microchannel geometrical designs and the application of exogenous energy, adhering to the principles of fluid motion. Consequently, this enables reproducible control over critical quality attributes (CQAs), such as particle size and distribution, encapsulation efficiency, drug loading, in vitro and in vivo drug delivery profiles, Zeta potential, and targeting capabilities, for micro/nanoparticle DDSs. In this review, we categorize microfluidic techniques and explore recent research developments in novel microchannel structures spanning the past 5 years (2018–2023) and their applications in micro/nanoparticle DDSs. Additionally, we elucidate the latest manipulation strategies of microfluidic techniques that impact foundational structures related to the CQAs of micro/nanoparticle DDSs. Furthermore, we offer insights into the industrial applications and challenges microfluidic techniques face in the context of novel micro/nanoparticle DDSs.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"91 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141105905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Tumor Targeting Biomimetic Drug Delivery Systems: A Promising Approach for Antitumor Therapy 肿瘤靶向生物仿生给药系统的进展：一种前景广阔的抗肿瘤疗法

Pharmaceutical Fronts Pub Date : 2024-05-22 DOI: 10.1055/s-0044-1786681

Ziyi Mo, Jiao He, Man Li, Rong Guo, Qin He

引用次数: 0

3D Printing Pharmaceuticals: Current Status and Future Opportunities 3D 打印药品：现状与未来机遇

Pharmaceutical Fronts Pub Date : 2024-04-05 DOI: 10.1055/s-0044-1782512

Senping Cheng, Timothy S. Tracy, Xiaoling Li

引用次数: 0

Discovery of Topoisomerase I Inhibitor Nitidine Derivatives with IL-10 Enhancing Activity for the Treatment of Sepsis 发现具有 IL-10 增强活性的拓扑异构酶 I 抑制剂硝啶衍生物，用于治疗败血症

Pharmaceutical Fronts Pub Date : 2024-03-07 DOI: 10.1055/s-0044-1780496

Siyu Liu, Yanting Pang, Zeng Zhao, Qingyan Sun

{"title":"Discovery of Topoisomerase I Inhibitor Nitidine Derivatives with IL-10 Enhancing Activity for the Treatment of Sepsis","authors":"Siyu Liu, Yanting Pang, Zeng Zhao, Qingyan Sun","doi":"10.1055/s-0044-1780496","DOIUrl":"https://doi.org/10.1055/s-0044-1780496","url":null,"abstract":"Nitidine chloride (NC) is a natural product that promotes the expression of interleukin-10 (IL-10) in macrophages by inhibiting topoisomerase I (TopoI) under stimulation by lipopolysaccharides (LPSs) and can be used in the treatment of sepsis. However, NC's poor water solubility limits its applications. This study aimed to design and synthesize a series of derivatives by simplifying the A- and E-rings in the structure of NC and introducing oxygen-containing groups, using NC as the lead compound. In this work, the ability of NC and its derivatives to induce IL-10 secretion and inhibit TopoI was evaluated. The water solubility of the compounds was determined in phosphate-buffered saline. An LPS-induced sepsis in mice was prepared to assess the activity of the compounds in vivo. Our data suggested that compound 6F showed better activity in inducing IL-10 secretion and inhibiting TopoI, and its water solubility was at least 500-fold higher than that of NC. When septic mice were given 6F (3 mg/kg), their survival rate was comparable to those treated with NC. Based on our findings, 6F may be a new drug candidate for the treatment of sepsis.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"13 69","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140260570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sequencing, Physiological Regulation, and Representative Disease Research Progress of RNA m6A Modification RNA m6A修饰的测序、生理调控和代表性疾病研究进展

Pharmaceutical Fronts Pub Date : 2024-03-01 DOI: 10.1055/s-0044-1780506

Xiaoqian Chen, Yuanyuan Li, Youfang Gan, Yuyang Guo, Hongling Zhou, Rui Wang

{"title":"Sequencing, Physiological Regulation, and Representative Disease Research Progress of RNA m6A Modification","authors":"Xiaoqian Chen, Yuanyuan Li, Youfang Gan, Yuyang Guo, Hongling Zhou, Rui Wang","doi":"10.1055/s-0044-1780506","DOIUrl":"https://doi.org/10.1055/s-0044-1780506","url":null,"abstract":"To date, more than 150 chemical modifications have been disclosed in different RNA species, which are employed to diversify the structure and function of RNA in living organisms. The N\u0000 6-methyladenosine (m6A) modification, which is found in the adenosine N\u0000 6 site of RNA, has been demonstrated to be the most heavy modification in the mRNA in cells. Moreover, the m6A modification in mRNAs of mammalian and other eukaryotic cells is highly conserved and mandatorily encoded. Increasing evidence indicates that the m6A modification plays a pivotal role in gene-expression regulation and cell-fate decisions. Here, we summarize the most recent m6A-sequencing technology, as well as the molecular mechanism underlying its occurrence, development, and potential use as a target for the treatment of human diseases. Furthermore, our review highlights other newly discovered chemical modifications of RNA that are associated with human disease, as well as their underlying molecular mechanisms. Thus, significant advancements have been made in qualitative/quantitative m6A detection and high-throughput sequencing, and research linking this RNA modification to disease. Efforts toward simplified and more accessible chemical/biological technologies that contribute to precision medicine are ongoing, to benefit society and patients alike.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"16 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140268718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient and Scalable Enantioselective Synthesis of a Key Intermediate for Rimegepant: An Oral CGRP Receptor Antagonist 高效、可扩展地对映体选择性合成 Rimegepant 的关键中间体：一种口服 CGRP 受体拮抗剂

Pharmaceutical Fronts Pub Date : 2024-03-01 DOI: 10.1055/s-0044-1780495

Zhonghua Luo, Guodong Sun, Guowei Wang, Xin Zhang, Yang Zhang, Ji Zhang

引用次数: 0

Electrochemical Construction of C–S Bond: A Green Approach for Preparing Sulfur-Containing Scaffolds 电化学构建 C-S 键：制备含硫支架的绿色方法

Pharmaceutical Fronts Pub Date : 2024-03-01 DOI: 10.1055/s-0044-1780505

Ruonan Zou, Jingbo Yu, P. Ying

引用次数: 0

Quality by Design Approach for Development and Characterization of Granisetron Hydrochloride-Loaded Orodispersible Films 盐酸格拉司琼负载型可分散薄膜的开发和表征质量设计方法

Pharmaceutical Fronts Pub Date : 2023-12-01 DOI: 10.1055/s-0043-1777043

Ming-Yan Li, Bing Wang, Jun-Qi Zhang, Liu-Liu Yang, Jun-Tao He, Fang Chen

{"title":"Quality by Design Approach for Development and Characterization of Granisetron Hydrochloride-Loaded Orodispersible Films","authors":"Ming-Yan Li, Bing Wang, Jun-Qi Zhang, Liu-Liu Yang, Jun-Tao He, Fang Chen","doi":"10.1055/s-0043-1777043","DOIUrl":"https://doi.org/10.1055/s-0043-1777043","url":null,"abstract":"Granisetron hydrochloride can be used to prevent and treat nausea and vomiting induced by chemotherapy. Its prolonged half-life and reduced dose requirement improve patient acceptance. However, patients undergoing chemotherapy often suffer from dysphagia and drug spitting due to emesis. Hence, the development of a patient-centered formulation of granisetron hydrochloride with simple medication and high compliance is crucial. The current study employed a polymer combination of polyvinylpyrrolidone/polyvinyl alcohol (PVP/PVA) as film-forming materials and Lycoat® RS 780 as a disintegrant to formulate orodispersible films (ODFs) loaded with granisetron hydrochloride. Guided by the concept of quality by design, the quality target product profile and critical quality attributes (CQAs) for the ODF were defined. Through the quality risk assessment, essential factors that have a significant impact on CQAs were identified. The formulation was screened using the Box–Behnken statistical design with three factors and three levels. Our data suggested that all ODF formulations exhibited a disintegration time of less than 60 seconds and complete dissolution within 5 minutes. Furthermore, the formulation displayed appropriate mechanical properties, water residue, and pH values. Thus, the granisetron hydrochloride-loaded ODF is regarded as a patient-friendly formulation that enhances compliance and consequently aids in therapeutic effectiveness.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":" 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138617465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0