Archives of Pharmacal Research最新文献_第6页

Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application 黄芪：植物学、植物化学、药理学和临床应用综述。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-03-16 DOI: 10.1007/s12272-024-01489-y

Ya-Xiao Liu, Xiao-Mei Song, Lin-Wei Dan, Jia-Mei Tang, Yi Jiang, Chong Deng, Dong-Dong Zhang, Yu-Ze Li, Wei Wang

{"title":"Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application","authors":"Ya-Xiao Liu, Xiao-Mei Song, Lin-Wei Dan, Jia-Mei Tang, Yi Jiang, Chong Deng, Dong-Dong Zhang, Yu-Ze Li, Wei Wang","doi":"10.1007/s12272-024-01489-y","DOIUrl":"10.1007/s12272-024-01489-y","url":null,"abstract":"<div>Astragali Radix (A. Radix) is the dried root of Astragalus membranaceus var. mongholicus (Bge) Hsiao or Astragalus membranaceus (Fisch.) Bge., belonging to the family Leguminosae, which is mainly distributed in China. A. Radix has been consumed as a tonic in China for more than 2000 years because of its medicinal effects of invigorating the spleen and replenishing qi. Currently, more than 400 natural compounds have been isolated and identified from A. Radix, mainly including saponins, flavonoids, phenylpropanoids, alkaloids, and others. Modern pharmacological studies have shown that A. Radix has anti-tumor, anti-inflammatory, immunomodulatory, anti-atherosclerotic, cardioprotective, anti-hypertensive, and anti-aging effects. It has been clinically used in the treatment of tumors, cardiovascular diseases, and cerebrovascular complications associated with diabetes with few side effects and high safety. This paper reviewed the progress of research on its chemical constituents, pharmacological effects, clinical applications, developing applications, and toxicology, which provides a basis for the better development and utilization of A. Radix.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 3","pages":"165 - 218"},"PeriodicalIF":6.9,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139874","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

Indole-3-acetic acid ameliorates dextran sulfate sodium-induced colitis via the ERK signaling pathway 吲哚-3-乙酸通过 ERK 信号通路改善右旋糖酐硫酸钠诱导的结肠炎。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-03-15 DOI: 10.1007/s12272-024-01488-z

Xinyan Qu, Yingying Song, Qingjun Li, Qi Xu, Yanru Li, Huimin Zhang, Xuemei Cheng, Charles R. Mackay, Quanbo Wang, Wei Liu

{"title":"Indole-3-acetic acid ameliorates dextran sulfate sodium-induced colitis via the ERK signaling pathway","authors":"Xinyan Qu, Yingying Song, Qingjun Li, Qi Xu, Yanru Li, Huimin Zhang, Xuemei Cheng, Charles R. Mackay, Quanbo Wang, Wei Liu","doi":"10.1007/s12272-024-01488-z","DOIUrl":"10.1007/s12272-024-01488-z","url":null,"abstract":"<div>Microbiota-derived catabolism of nutrients is closely related to ulcerative colitis (UC). The level of indole-3-acetic acid (IAA), a microbiota-dependent metabolite of tryptophan, was decreased significantly in the feces of UC patients. Thus supplementation with IAA could be a potential therapeutic method for ameliorating colitis. In this work, the protective effect of supplementation with IAA on dextran sulfate sodium (DSS)-induced colitis was evaluated, and the underlying mechanism was elucidated. The results indicated that the administration of IAA significantly relieved DSS-induced weight loss, reduced the disease activity index (DAI), restored colon length, alleviated intestinal injury, and improved the intestinal tight junction barrier. Furthermore, IAA inhibited intestinal inflammation by reducing the expression of proinflammatory cytokines and promoting the production of IL-10 and TGF-β1. In addition, the ERK signaling pathway is an important mediator of various physiological processes including inflammatory responses and is closely associated with the expression of IL-10. Notably, IAA treatment induced the activation of extracellular signal-regulated kinase (ERK), which is involved in the progression of colitis, while the ERK inhibitor U0126 attenuated the beneficial effects of IAA. In summary, IAA could attenuate the clinical symptoms of colitis, and the ERK signaling pathway was involved in the underlying mechanism. Supplementation with IAA could be a potential option for preventing or ameliorating UC.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 3","pages":"288 - 299"},"PeriodicalIF":6.9,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136410","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

The potential of therapeutic strategies targeting mitochondrial biogenesis for the treatment of insulin resistance and type 2 diabetes mellitus 针对线粒体生物生成的治疗策略在治疗胰岛素抵抗和 2 型糖尿病方面的潜力。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-03-14 DOI: 10.1007/s12272-024-01490-5

Wenwen Ding, Xiaoxue Yang, Kaiyi Lai, Yu Jiang, Ying Liu

{"title":"The potential of therapeutic strategies targeting mitochondrial biogenesis for the treatment of insulin resistance and type 2 diabetes mellitus","authors":"Wenwen Ding, Xiaoxue Yang, Kaiyi Lai, Yu Jiang, Ying Liu","doi":"10.1007/s12272-024-01490-5","DOIUrl":"10.1007/s12272-024-01490-5","url":null,"abstract":"<div>Type 2 diabetes mellitus (T2DM) is a persistent metabolic disorder marked by deficiencies in insulin secretion and/or function, affecting various tissues and organs and leading to numerous complications. Mitochondrial biogenesis, the process by which cells generate new mitochondria utilizing existing ones plays a crucial role in energy homeostasis, glucose metabolism, and lipid handling. Recent evidence suggests that promoting mitochondrial biogenesis can alleviate insulin resistance in the liver, adipose tissue, and skeletal muscle while improving pancreatic β-cell function. Moreover, enhanced mitochondrial biogenesis has been shown to ameliorate T2DM symptoms and may contribute to therapeutic effects for the treatment of diabetic nephropathy, cardiomyopathy, retinopathy, and neuropathy. This review summarizes the intricate connection between mitochondrial biogenesis and T2DM, highlighting the potential of novel therapeutic strategies targeting mitochondrial biogenesis for T2DM treatment and its associated complications. It also discusses several natural products that exhibit beneficial effects on T2DM by promoting mitochondrial biogenesis.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 3","pages":"219 - 248"},"PeriodicalIF":6.9,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130606","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

New autophagy-modulating lanostane-type triterpenoids from a hallucinogenic poisonous mushroom Gymnopilus orientispectabilis 从一种致幻毒蘑菇Gymnopilus orientispectabilis中提取的新型自噬调节羊齿甾类三萜类化合物。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-02-28 DOI: 10.1007/s12272-024-01486-1

Seulah Lee, Mina Jang, Rhim Ryoo, Jongtae Roh, Sung-Kyun Ko, Ki Hyun Kim

{"title":"New autophagy-modulating lanostane-type triterpenoids from a hallucinogenic poisonous mushroom Gymnopilus orientispectabilis","authors":"Seulah Lee, Mina Jang, Rhim Ryoo, Jongtae Roh, Sung-Kyun Ko, Ki Hyun Kim","doi":"10.1007/s12272-024-01486-1","DOIUrl":"10.1007/s12272-024-01486-1","url":null,"abstract":"<div>Gymnopilus orientispectabilis, also known as “big laughter mushroom,” is a hallucinogenic poisonous mushroom that causes excessive laughter upon ingestion. From the fruiting bodies of G. orientispectabilis, eight lanostane-type triterpenoids (1–8), including seven novel compounds: gymnojunols A-G (2–8), were isolated. The chemical structures of these new compounds (2–8) were determined by analyzing their 1D and 2D NMR spectra and HR-EISMS, and their absolute configurations were unambiguously assigned by quantum chemical ECD calculations and a computational method coupled with a statistical procedure (DP4+). Upon evaluating autophagic activity, compounds 2, 6, and 7 increased LC3B-II levels in HeLa cells to a similar extent as bafilomycin, an autophagy inhibitor. In contrast, compound 8 decreased the levels of both LC3B-I and LC3B-II, and a similar effect was observed following treatment with rapamycin, an autophagy inducer. Our findings provide experimental evidence for new potential autophagy modulators in the hallucinogenic poisonous mushroom G. orientispectabilis.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 3","pages":"272 - 287"},"PeriodicalIF":6.9,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982151","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

Prenylated flavonoid fractions from Glycyrrhiza glabra alleviate insulin resistance in HepG2 cells by regulating the ERK/IRS-1 and PI3K/Akt signaling pathways 甘草中的异戊烯基黄酮提取物通过调节 ERK/IRS-1 和 PI3K/Akt 信号通路减轻 HepG2 细胞的胰岛素抵抗。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-01-24 DOI: 10.1007/s12272-024-01485-2

Defeng Li, Jinling Fan, Lin Du, Guoyan Ren

{"title":"Prenylated flavonoid fractions from Glycyrrhiza glabra alleviate insulin resistance in HepG2 cells by regulating the ERK/IRS-1 and PI3K/Akt signaling pathways","authors":"Defeng Li, Jinling Fan, Lin Du, Guoyan Ren","doi":"10.1007/s12272-024-01485-2","DOIUrl":"10.1007/s12272-024-01485-2","url":null,"abstract":"<div>Insulin resistance (IR) is a key factor in the pathogenesis of disrupted glucose metabolism. Although the extract of Glycyrrhiza glabra has shown significant hypoglycemic activity, its bioactive components remain to be identified, and their mechanisms of action, especially on hepatocyte glucose metabolism, are yet to be explored. In the present study, the primary compounds from Glycyrrhiza glabra [named prenylated flavonoid fractions (PFFs)] have been identified and their chemical structures have been elucidated. The therapeutic effects of PFFs extracted from G. glabra on glucose metabolism disorders and IR in high insulin-induced insulin-resistant HepG2 (IR-HepG2) cells have been determined. Glabridin (GLD) was used as a control. The results indicated that, similar to GLD, PFFs increased glucose consumption, glucose uptake, and translocation of glucose transporter 4 to the plasma membrane in IR-HepG2 cells. In addition, they enhanced the activities of glycogen synthase, glucokinase, and pyruvate kinase, while reducing the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Furthermore, they activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and suppressed the extracellular signal-regulated kinase/insulin receptor substrate-1 (ERK/IRS-1) pathway. These findings suggest that, similar to GLD, PFFs can alleviate impaired glucose metabolism and alleviate IR in IR-HepG2 cells.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.The authors and their affiliations have been confirmed as correct.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 2","pages":"127 - 145"},"PeriodicalIF":6.9,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545461","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

Herbal medicine and gut microbiota: exploring untapped therapeutic potential in neurodegenerative disease management 草药和肠道微生物群：探索神经退行性疾病治疗中尚未开发的治疗潜力。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-01-15 DOI: 10.1007/s12272-023-01484-9

Yueyue Guan, Guohua Tang, Lei Li, Jianzhong Shu, Yuhua Zhao, Li Huang, Jun Tang

{"title":"Herbal medicine and gut microbiota: exploring untapped therapeutic potential in neurodegenerative disease management","authors":"Yueyue Guan, Guohua Tang, Lei Li, Jianzhong Shu, Yuhua Zhao, Li Huang, Jun Tang","doi":"10.1007/s12272-023-01484-9","DOIUrl":"10.1007/s12272-023-01484-9","url":null,"abstract":"<div>The gut microbiota that exists in the human gastrointestinal tract is incredibly important for the maintenance of general health as it contributes to multiple aspects of host physiology. Recent research has revealed a dynamic connection between the gut microbiota and the central nervous system, that can influence neurodegenerative diseases (NDs). Indeed, imbalances in the gut microbiota, or dysbiosis, play a vital role in the pathogenesis and progression of human diseases, particularly NDs. Herbal medicine has been used for centuries to treat human diseases, including NDs. These compounds help to relieve symptoms and delay the progression of NDs by improving intestinal barrier function, reducing neuroinflammation, and modulating neurotransmitter production. Notably, herbal medicine can mitigate the progression of NDs by regulating the gut microbiota. Therefore, an in-depth understanding of the potential mechanisms by which herbal medicine regulates the gut microbiota in the treatment of NDs can help explain the pathogenesis of NDs from a novel perspective and propose novel therapeutic strategies for NDs. In this review, we investigate the potential neuroprotective effects of herbal medicine, focusing on its ability to regulate the gut microbiota and restore homeostasis. We also highlight the challenges and future research priorities of the integration of herbal medicine and modern medicine. As the global population ages, access to this information is becoming increasingly important for developing effective treatments for these diseases.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 2","pages":"146 - 164"},"PeriodicalIF":6.9,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10830735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472133","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

Comparative metabolism of aschantin in human and animal hepatocytes 人类和动物肝细胞中aschantin的代谢比较。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2024-01-05 DOI: 10.1007/s12272-023-01483-w

Min Seo Lee, Hyun Joo Shim, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Im-Sook Song, Hye Suk Lee

{"title":"Comparative metabolism of aschantin in human and animal hepatocytes","authors":"Min Seo Lee, Hyun Joo Shim, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Im-Sook Song, Hye Suk Lee","doi":"10.1007/s12272-023-01483-w","DOIUrl":"10.1007/s12272-023-01483-w","url":null,"abstract":"<div>Aschantin, a tetrahydrofurofuran lignan with a 1,3-benzodioxole group derived from Flos Magnoliae, exhibits antioxidant, anti-inflammatory, cytotoxic, and antimicrobial activities. This study compared the metabolic profiles of aschantin in human, dog, mouse, and rat hepatocytes using liquid chromatography–high-resolution mass spectrometry. The hepatic extraction ratio of aschantin among the four species was 0.46–0.77, suggesting that it undergoes a moderate-to-extensive degree of hepatic metabolism. Hepatocyte incubation of aschantin produced 4 phase 1 metabolites, including aschantin catechol (M1), O-desmethylaschantin (M2 and M3), and hydroxyaschantin (M4), and 14 phase 2 metabolites, including O-methyl-M1 (M5 and M6) via catechol O-methyltransferase (COMT), six glucuronides of M1, M2, M3, M5, and M6, and six sulfates of M1, M2, M3, M5, and M6. Enzyme kinetic studies using aschantin revealed that the production of M1, a major metabolite, via O-demethylenation is catalyzed by cytochrome 2C8 (CYP2C8), CYP2C9, CYP2C19, CYP3A4, and CYP3A5 enzymes; the formation of M2 (O-desmethylaschantin) is catalyzed by CYP2C9 and CYP2C19; and the formation of M4 is catalyzed by CYP3A4 enzyme. Two glutathione (GSH) conjugates of M1 were identified after incubation of aschantin with human and animal liver microsomes in the presence of nicotinamide adenine dinucleotide phosphate and GSH, but they were not detected in the hepatocytes of all species. In conclusion, aschantin is extensively metabolized, producing 18 metabolites in human and animal hepatocytes catalyzed by CYP, COMT, UDP-glucuronosyltransferase, and sulfotransferase. These results can help in clarifying the involvement of metabolizing enzymes in the pharmacokinetics and drug interactions of aschantin and in elucidating GSH conjugation associated with the reactive intermediate formed from M1 (aschantin catechol).</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 2","pages":"111 - 126"},"PeriodicalIF":6.9,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139105711","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 pitavastatin in relation to SLCO1B1 genetic polymorphism 基于生理学的匹伐他汀药代动力学（PBPK）模型与 SLCO1B1 基因多态性的关系

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-30 DOI: 10.1007/s12272-023-01476-9

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

{"title":"Physiologically based pharmacokinetic (PBPK) modeling of pitavastatin in relation to SLCO1B1 genetic polymorphism","authors":"Chang-Keun Cho, Ju Yeon Mo, Eunvin Ko, Pureum Kang, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Jung-Woo Bae, Chang-Ik Choi","doi":"10.1007/s12272-023-01476-9","DOIUrl":"10.1007/s12272-023-01476-9","url":null,"abstract":"<div>Pitavastatin, a potent 3-hydroxymethylglutaryl coenzyme A reductase inhibitor, is indicated for the treatment of hypercholesterolemia and mixed dyslipidemia. Hepatic uptake of pitavastatin is predominantly occupied by the organic anion transporting polypeptide 1B1 (OATP1B1) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, which is a polymorphic gene that encodes OATP1B1. SLCO1B1 genetic polymorphism significantly alters the pharmacokinetics of pitavastatin. This study aimed to establish the physiologically based pharmacokinetic (PBPK) model to predict pitavastatin pharmacokinetics according to SLCO1B1 genetic polymorphism. PK-Sim® version 10.0 was used to establish the whole-body PBPK model of pitavastatin. Our pharmacogenomic data and a total of 27 clinical pharmacokinetic data with different dose administration and demographic properties were used to develop and validate the model, respectively. Physicochemical properties and disposition characteristics of pitavastatin were acquired from previously reported data or optimized to capture the plasma concentration–time profiles in different SLCO1B1 diplotypes. Model evaluation was performed by comparing the predicted pharmacokinetic parameters and profiles to the observed data. Predicted plasma concentration–time profiles were visually similar to the observed profiles in the non-genotyped populations and different SLCO1B1 diplotypes. All fold error values for AUC and Cmax were included in the two fold range of observed values. Thus, the PBPK model of pitavastatin in different SLCO1B1 diplotypes was properly established. The present study can be useful to individualize the dose administration strategy of pitavastatin in individuals with various ages, races, and SLCO1B1 diplotypes.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 2","pages":"95 - 110"},"PeriodicalIF":6.9,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139068232","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

Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions 癌症治疗中的抗体-药物共轭物：创新、挑战和未来方向。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-28 DOI: 10.1007/s12272-023-01479-6

Shivangi Kumari, Sonam Raj, M. Arockia Babu, Gurjit Kaur Bhatti, Jasvinder Singh Bhatti

{"title":"Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions","authors":"Shivangi Kumari, Sonam Raj, M. Arockia Babu, Gurjit Kaur Bhatti, Jasvinder Singh Bhatti","doi":"10.1007/s12272-023-01479-6","DOIUrl":"10.1007/s12272-023-01479-6","url":null,"abstract":"<div>The emergence of antibody-drug conjugates (ADCs) as a potential therapeutic avenue in cancer treatment has garnered significant attention. By combining the selective specificity of monoclonal antibodies with the cytotoxicity of drug molecules, ADCs aim to increase the therapeutic index, selectively targeting cancer cells while minimizing systemic toxicity. Various ADCs have been licensed for clinical usage, with ongoing research paving the way for additional options. However, the manufacture of ADCs faces several challenges. These include identifying suitable target antigens, enhancing antibodies, linkers, and payloads, and managing resistance mechanisms and side effects. This review focuses on the strategies to overcome these hurdles, such as site-specific conjugation techniques, novel antibody formats, and combination therapy. Our focus lies on current advancements in antibody engineering, linker technology, and cytotoxic payloads while addressing the challenges associated with ADC development. Furthermore, we explore the future potential of personalized medicine, leveraging individual patients’ molecular profiles, to propel ADC treatments forward. As our understanding of the molecular mechanisms driving cancer progression continues to expand, we anticipate the development of new ADCs that offer more effective and personalized therapeutic options for cancer patients.</div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 1","pages":"40 - 65"},"PeriodicalIF":6.9,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048237","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

PBPK modeling to predict the pharmacokinetics of pantoprazole in different CYP2C19 genotypes 通过 PBPK 模型预测不同 CYP2C19 基因型的泮托拉唑的药代动力学。

IF 6.9 3区医学

Archives of Pharmacal Research Pub Date : 2023-12-27 DOI: 10.1007/s12272-023-01478-7

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

{"title":"PBPK modeling to predict the pharmacokinetics of pantoprazole in different CYP2C19 genotypes","authors":"Chang-Keun Cho, Eunvin Ko, Ju Yeon Mo, Pureum Kang, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee, Jung-Woo Bae, Chang-Ik Choi","doi":"10.1007/s12272-023-01478-7","DOIUrl":"10.1007/s12272-023-01478-7","url":null,"abstract":"<div>Pantoprazole is used to treat gastroesophageal reflux disease (GERD), maintain healing of erosive esophagitis (EE), and control symptoms related to Zollinger–Ellison syndrome (ZES). Pantoprazole is mainly metabolized by cytochrome P450 (CYP) 2C19, converting to 4′-demethyl pantoprazole. CYP2C19 is a genetically polymorphic enzyme, and the genetic polymorphism affects the pharmacokinetics and/or pharmacodynamics of pantoprazole. In this study, we aimed to establish the physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of pantoprazole in populations with various CYP2C19 metabolic activities. A comprehensive investigation of previous reports and drug databases was conducted to collect the clinical pharmacogenomic data, physicochemical data, and disposition properties of pantoprazole, and the collected data were used for model establishment. The model was evaluated by comparing the predicted plasma concentration–time profiles and/or pharmacokinetic parameters (AUC and Cmax) with the clinical observation results. The predicted plasma concentration–time profiles in different CYP2C19 phenotypes properly captured the observed profiles. All fold error values for AUC and Cmax were included in the two-fold range. Consequently, the minimal PBPK model for pantoprazole related to CYP2C19 genetic polymorphism was properly established and it can predict the pharmacokinetics of pantoprazole in different CYP2C19 phenotypes. The present model can broaden the insight into the individualized pharmacotherapy for pantoprazole. </div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 1","pages":"82 - 94"},"PeriodicalIF":6.9,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039429","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