Archives of Pharmacal Research最新文献_第3页

Discovery of novel naphthalene-based diarylamides as pan-Raf kinase inhibitors with promising anti-melanoma activity: rational design, synthesis, in vitro and in silico screening 新型萘基二芳酰胺作为泛raf激酶抑制剂具有抗黑色素瘤活性的发现：合理设计，合成，体外和硅筛选。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2025-02-08 DOI: 10.1007/s12272-025-01533-5

Ahmed Elkamhawy, Usama M. Ammar, Minkyoung Kim, Anam Rana Gul, Tae Jung Park, Kyeong Lee

{"title":"Discovery of novel naphthalene-based diarylamides as pan-Raf kinase inhibitors with promising anti-melanoma activity: rational design, synthesis, in vitro and in silico screening","authors":"Ahmed Elkamhawy, Usama M. Ammar, Minkyoung Kim, Anam Rana Gul, Tae Jung Park, Kyeong Lee","doi":"10.1007/s12272-025-01533-5","DOIUrl":"10.1007/s12272-025-01533-5","url":null,"abstract":"<div>Raf kinase enzymes are often dysregulated in melanoma. While sorafenib demonstrates strong activity against wild-type B-Raf, it fails to effectively inhibit the mutated form of B-Raf. In this study, sorafenib served as a lead compound for the development of new derivatives designed to enhance inhibitory activity across multiple Raf isoforms (pan-Raf inhibitors). Novel naphthalene-based diarylamide derivatives were subsequently designed, synthesized, and evaluated for their biological activity against various Raf kinase isoforms and the melanoma A375 cell line. Among these, compound 9a, containing a difluoromethoxy group, demonstrated strong inhibitory activity across B-RafWT, B-RafV600E, and c-Raf. Additionally, it induced G2/M phase arrest and triggered dose-dependent apoptosis, effectively suppressing both cell proliferation and survival. Compound 9a also exhibited high selectivity for Raf isoforms with minimal off-target effects, underscoring its specificity and therapeutic potential for Raf-driven malignancies.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 2","pages":"150 - 165"},"PeriodicalIF":6.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-025-01533-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation 活性氧介导的炎性体活化对肿瘤微环境的调节。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2025-01-31 DOI: 10.1007/s12272-025-01532-6

Jeong-Hoon Jang, Do-Hee Kim, Kyung-Soo Chun

{"title":"Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation","authors":"Jeong-Hoon Jang, Do-Hee Kim, Kyung-Soo Chun","doi":"10.1007/s12272-025-01532-6","DOIUrl":"10.1007/s12272-025-01532-6","url":null,"abstract":"<div>Tumor microenvironment (TME) is composed of diverse cell types whose interactions, both direct and indirect, significantly influence tumorigenesis and therapeutic outcomes. Within TME, reactive oxygen species (ROS) are produced by various cells and exhibit a dual role: moderate ROS levels promote tumor initiation and progression, whereas excessive levels induce cancer cell death, influencing the efficacy of anticancer therapies. Inflammasomes, cytosolic multiprotein complexes, are pivotal in multiple stages of tumorigenesis and play a crucial role in establishing the inflammatory TME. By releasing cytokines such as IL-1β and IL-18, inflammasomes contribute to immune cell recruitment and sustain a chronic inflammatory state that supports tumor growth. ROS are critical regulators of inflammasome activation, with the impact of ROS-mediated activation differing across cell types, leading to distinct influences on tumor progression and therapeutic responses. This review explores how ROS drive inflammasome activation in various TME-associated cells and the reciprocal ROS generation induced by inflammasomes, examining their multifaceted impact on tumorigenesis and therapeutic efficacy. By elucidating the complex interplay between ROS and inflammasomes in TME, we provide insights into potential therapeutic approaches that could modulate cancer progression and enhance treatment outcomes.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 2","pages":"115 - 131"},"PeriodicalIF":6.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Physiologically based pharmacokinetic (PBPK) modeling of gliclazide for different genotypes of CYP2C9 and CYP2C19 格列齐特对不同基因型CYP2C9和CYP2C19的生理药代动力学（PBPK）建模

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2025-01-06 DOI: 10.1007/s12272-024-01528-8

Hye-Jung Park, Sang-Ho Lee, Pureum Kang, Chang‑Keun Cho, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Jung‑Woo Bae, Chang-Ik Choi

{"title":"Physiologically based pharmacokinetic (PBPK) modeling of gliclazide for different genotypes of CYP2C9 and CYP2C19","authors":"Hye-Jung Park, Sang-Ho Lee, Pureum Kang, Chang‑Keun Cho, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Jung‑Woo Bae, Chang-Ik Choi","doi":"10.1007/s12272-024-01528-8","DOIUrl":"10.1007/s12272-024-01528-8","url":null,"abstract":"<div>Gliclazide is a sulfonylurea hypoglycemic agent used to treat type 2 diabetes. Cytochrome P450 (CYP) 2C9 and CYP2C19 are primarily involved in the hepatic metabolism of gliclazide. The two CYP isozymes are highly polymorphic, and their genetic polymorphisms are known to significantly impact the pharmacokinetics of gliclazide. In the present study, the physiologically based pharmacokinetic (PBPK) model was developed using data from subjects whose pharmacokinetic parameters were influenced by the genetic polymorphisms of the CYP metabolic enzymes. All predicted plasma concentration–time profiles generated by the model showed visual agreement with the observed data, and the pharmacokinetic results were within the twofold error range. Individual simulation results showed additional metrics: average fold error (− 0.19 to 0.07), geometric mean fold error (1.13–1.56), and mean relative deviation (1.18–1.58) for AUC, Cmax, T1/2, Tmax, CL/F, and Vd values. These results met the standard evaluation criteria. The validation across a total of 8 studies and 7 races also satisfied the twofold error range for AUC, Cmax, and T1/2. Therefore, variations in gliclazide exposure according to individuals’ CYP2C9 and CYP2C19 genotypes were properly captured through PBPK modeling in this study. This PBPK model may allow us to predict the gliclazide pharmacokinetics of patients with genetic polymorphisms in CYP2C9 and CYPC19 under various conditions, ultimately contributing to the realization of individualized drug therapy.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 3","pages":"234 - 250"},"PeriodicalIF":6.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Canine mammary tumors as a promising adjunct preclinical model for human breast cancer research: similarities, opportunities, and challenges 犬乳腺肿瘤作为人类乳腺癌研究的有前途的辅助临床前模型：相似性，机遇和挑战。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2025-01-03 DOI: 10.1007/s12272-024-01524-y

Zeeshan Ahmad Bhutta, Kyung-Chul Choi

{"title":"Canine mammary tumors as a promising adjunct preclinical model for human breast cancer research: similarities, opportunities, and challenges","authors":"Zeeshan Ahmad Bhutta, Kyung-Chul Choi","doi":"10.1007/s12272-024-01524-y","DOIUrl":"10.1007/s12272-024-01524-y","url":null,"abstract":"<div>Despite significant progress in the field of human breast cancer research and treatment, there is a consistent increase in the incidence rate of 0.5 percent annually, posing challenges in the development of effective novel therapeutic strategies. The failure rate of drugs in clinical trials stands at approximately 95%, primarily attributed to the limitations and lack of reliability of existing preclinical models, such as mice, which do not mimic human tumor biology. This article examines the potential utility of canine mammary tumors as an adjunct preclinical model for investigating human breast cancer. Given the numerous similarities between canine and human breast cancer, canines present a promising alternative model. The discussion delves into the intricate molecular and clinical aspects of human breast cancer and canine mammary tumors, shedding light on the tumors' molecular profiles, identifying specific molecular markers, and the application of radiological imaging modalities. Furthermore, the manuscript addresses the current constraints of preclinical cancer studies, the benefits of using canines as models, and the obstacles linked to the canine mammary tumors model. By concentrating on these elements, this review aims to highlight the viability of canine models in enhancing our understanding and management of human breast cancer.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 1","pages":"43 - 61"},"PeriodicalIF":6.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Retraction Note: MiR-338-5p ameliorates pathological cardiac hypertrophy by targeting CAMKIIδ 注：MiR-338-5p通过靶向CAMKIIδ改善病理性心肌肥厚。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2025-01-02 DOI: 10.1007/s12272-024-01530-0

Kailong Li, Yuedong Lin, Cong Li

引用次数: 0

Effects of fluconazole on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in different CYP2C9 genotypes 氟康唑对不同CYP2C9基因型塞来昔布及其羧酸代谢物药动学的影响

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-12-27 DOI: 10.1007/s12272-024-01531-z

Chang-Keun Cho, Pureum Kang, Choon-Gon Jang, Yun Jeong Lee, Jung-Woo Bae, Chang-Ik Choi, Seok-Yong Lee

{"title":"Effects of fluconazole on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in different CYP2C9 genotypes","authors":"Chang-Keun Cho, Pureum Kang, Choon-Gon Jang, Yun Jeong Lee, Jung-Woo Bae, Chang-Ik Choi, Seok-Yong Lee","doi":"10.1007/s12272-024-01531-z","DOIUrl":"10.1007/s12272-024-01531-z","url":null,"abstract":"<div>This study aimed to investigate the effects of fluconazole, a moderate inhibitor of CYP2C9 and CYP3A4, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in different CYP2C9 genotypes. A total of thirty-nine healthy Korean male volunteers were divided into three different CYP2C9 genotype groups (CYP2C9*1/*1, *1/*3 and *3/*3 genotypes) and were enrolled in the celecoxib alone trial, celecoxib with fluconazole trial, or both. In the celecoxib alone trial, participants received a single oral dose of 200 mg celecoxib. In the celecoxib with fluconazole trial, participants received 300 mg fluconazole on day 1, 150 mg fluconazole once daily for four consecutive days (day 2–5), and a coadministration of 200 mg celecoxib with 150 mg fluconazole on day 6. Plasma concentrations of celecoxib and celecoxib carboxylic acid were determined by using HPLC–MS/MS. In the CYP2C9*1/*1 genotype group, fluconazole treatment increased AUCinf of celecoxib by 2.61-fold, and decreased CL/F by 60.4% (both p < 0.001). In the CYP2C9*1/*3 genotype group, fluconazole treatment increased AUCinf of celecoxib by 2.44-fold (p < 0.001), prolonged t1/2 by 1.36-fold (p < 0.05), and decreased CL/F by 60.4% (p < 0.001). Fluconazole treatment increased AUCinf of celecoxib by 2.23-fold, prolonged t1/2 by 1.64-fold, and decreased CL/F by 53.8% in the subject with CYP2C9*3/*3 genotype. Cmax of celecoxib carboxylic acid significantly decreased in CYP2C9*1/*1 and *1/*3 genotypes (p < 0.01 and p < 0.05, respectively), following fluconazole treatment, whereas AUCinf showed no significant changes in any CYP2C9 genotype group. In conclusion, fluconazole affected the pharmacokinetics of celecoxib in different CYP2C9 genotypes.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 3","pages":"224 - 233"},"PeriodicalIF":6.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Immunosenescence and age-related immune cells: causes of age-related diseases 免疫衰老和与年龄有关的免疫细胞：与年龄有关的疾病的原因。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-12-26 DOI: 10.1007/s12272-024-01529-7

Nam-Hee Kim, So-Jin Sim, Hong-Gyu Han, Jeong-Hyuk Yoon, Yong-Hyun Han

引用次数: 0

Ideal animal models according to multifaceted mechanisms and peculiarities in neurological disorders: present and challenges 理想的动物模型，根据多方面的机制和特点在神经系统疾病：目前和挑战。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-12-18 DOI: 10.1007/s12272-024-01527-9

Shrawani Lamichhane, Jo-Eun Seo, Ji Hoon Jeong, Sooyeun Lee, Sangkil Lee

{"title":"Ideal animal models according to multifaceted mechanisms and peculiarities in neurological disorders: present and challenges","authors":"Shrawani Lamichhane, Jo-Eun Seo, Ji Hoon Jeong, Sooyeun Lee, Sangkil Lee","doi":"10.1007/s12272-024-01527-9","DOIUrl":"10.1007/s12272-024-01527-9","url":null,"abstract":"<div>Neurological disorders, encompassing conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), pose a significant global health challenge, affecting millions worldwide. With an aging population and increased life expectancy, the prevalence of these disorders is escalating rapidly, leading to substantial economic burdens exceeding trillions of dollars annually. Animal models play a crucial role in understanding the underlying mechanisms of these disorders and developing effective treatments. Various species, including rodents, non-human primates, and fruit flies, are utilized to replicate specific aspects of human neurological conditions. However, selecting the ideal animal model requires careful consideration of its proximity to human disease conditions and its ability to mimic disease pathobiology and pharmacological responses. An Animal Model Quality Assessment (AMQA) tool has been developed to facilitate this selection process, focusing on assessing models based on their similarity to human conditions and disease pathobiology. Therefore, integrating intrinsic and extrinsic factors linked to the disease into the study's objectives aids in constructing a biological information matrix for comparing disease progression between the animal model and human disease. Ultimately, selecting an ideal animal disease model depends on its predictive, face, and construct validity, ensuring relevance and reliability in translational research efforts.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 1","pages":"62 - 88"},"PeriodicalIF":6.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Three new xanthones and other anti-inflammatory components from the aerial parts of Hypericum beanii 从金丝桃地上部分离得到三种新的山酮类及其它抗炎成分。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-12-18 DOI: 10.1007/s12272-024-01526-w

Wei Ma, Fu-Cai Ren, Xue-Ru Wang, Ning Li

{"title":"Three new xanthones and other anti-inflammatory components from the aerial parts of Hypericum beanii","authors":"Wei Ma, Fu-Cai Ren, Xue-Ru Wang, Ning Li","doi":"10.1007/s12272-024-01526-w","DOIUrl":"10.1007/s12272-024-01526-w","url":null,"abstract":"<div>Hypericum beanii, a traditional folk medicine plant, has been employed in treating various inflammation-related diseases. In this study, three new prenylated xanthones, named beanigenin A (1), beanigenin B (2), and beanigenin C (3), along with twenty-five known compounds (4–28), were isolated from the aerial parts of H. beanii. The new xanthones were elucidated based on modern spectroscopic experiments, including nuclear magnetic resonance spectroscopy (NMR) techniques, high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and electronic circular dichroism (ECD). All the compounds were evaluated for their anti-inflammatory effects by measuring their inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Our findings showed that compounds 1–10, 12, 14, 21–23, 26, and 28 displayed significant anti-inflammatory effects, with IC50 values ranging from 0.82 to 9.71 μM. The MOE software was utilized to conduct an in silico evaluation of the potential inhibitory activity of the three new xanthones against inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) proteins. The results indicated that the three new xanthones demonstrated a high binding affinity with both iNOS and COX-2 proteins.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 1","pages":"89 - 101"},"PeriodicalIF":6.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cell membrane chromatography relative competitive method for the accurate determination of relative KD values of drug-receptor interactions 细胞膜色谱相对竞争法准确测定药物受体相互作用的相对KD值。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-12-10 DOI: 10.1007/s12272-024-01525-x

Panpan Lei, Weina Ma, Jiapan Gao, Bingxi Ren, Xiaoyu Ma, Yuxiu Zhang, Xinyue Su, Jinna Liang, Langchong He

{"title":"Cell membrane chromatography relative competitive method for the accurate determination of relative KD values of drug-receptor interactions","authors":"Panpan Lei, Weina Ma, Jiapan Gao, Bingxi Ren, Xiaoyu Ma, Yuxiu Zhang, Xinyue Su, Jinna Liang, Langchong He","doi":"10.1007/s12272-024-01525-x","DOIUrl":"10.1007/s12272-024-01525-x","url":null,"abstract":"<div>The specific binding of a drug to the receptor is a prerequisite for its action. The equilibrium dissociation constant (KD) is an important parameter for measuring the strength of drug-receptor interactions. Cell membrane chromatography (CMC) is a powerful way to determine the KD value; however, the common disadvantage is that the attenuation of biological activity with the analysis process leads to corresponding errors in comparing KD values of a series of drugs. Therefore, it is of practical significance to analyze the relative KD values of drugs for the same membrane receptor under the same conditions. We developed a CMC relative competitive method to determine the relative KD values of drugs through simultaneous injection of the control compound and analyte in each analysis, circumventing the error in KD values of drugs due to the attenuation of the biological activity of the CMC column. The results showed that the KD values of CD147 antagonists and MRGPRX2 agonists determined using the CMC relative competitive method correlated well with the KD values obtained via frontal analysis and stepwise frontal method using the CD147h (MRGPRX2h)/CMC system. Critically, the biological activities of the CD147 antagonists and MRGPRX2 agonists were significantly correlated with KD values measured using the CMC relative competitive method. Therefore, the CMC relative competitive method can accurately and efficiently evaluate the relative KD values of drugs and effectively predict the differences in pharmacological activity between a series of drugs, which has important guiding significance in the development of targeted drugs.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 1","pages":"102 - 114"},"PeriodicalIF":6.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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