{"title":"Advances in machine intelligence-driven virtual screening approaches for big-data","authors":"Neeraj Kumar, Vishal Acharya","doi":"10.1002/med.21995","DOIUrl":"10.1002/med.21995","url":null,"abstract":"<p>Virtual screening (VS) is an integral and ever-evolving domain of drug discovery framework. The VS is traditionally classified into ligand-based (LB) and structure-based (SB) approaches. Machine intelligence or artificial intelligence has wide applications in the drug discovery domain to reduce time and resource consumption. In combination with machine intelligence algorithms, VS has emerged into revolutionarily progressive technology that learns within robust decision orders for data curation and hit molecule screening from large VS libraries in minutes or hours. The exponential growth of chemical and biological data has evolved as “big-data” in the public domain demands modern and advanced machine intelligence-driven VS approaches to screen hit molecules from ultra-large VS libraries. VS has evolved from an individual approach (LB and SB) to integrated LB and SB techniques to explore various ligand and target protein aspects for the enhanced rate of appropriate hit molecule prediction. Current trends demand advanced and intelligent solutions to handle enormous data in drug discovery domain for screening and optimizing hits or lead with fewer or no false positive hits. Following the big-data drift and tremendous growth in computational architecture, we presented this review. Here, the article categorized and emphasized individual VS techniques, detailed literature presented for machine learning implementation, modern machine intelligence approaches, and limitations and deliberated the future prospects.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"939-974"},"PeriodicalIF":13.3,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Drugs/agents for the treatment of ischemic stroke: Advances and perspectives","authors":"Jian Jia, Weijie Jiao, Guan Wang, Jianbing Wu, Zhangjian Huang, Yihua Zhang","doi":"10.1002/med.22009","DOIUrl":"10.1002/med.22009","url":null,"abstract":"<p>Ischemic stroke (IS) poses a significant threat to global human health and life. In recent decades, we have witnessed unprecedented progresses against IS, including thrombolysis, thrombectomy, and a few medicines that can assist in reopening the blocked brain vessels or serve as standalone treatments for patients who are not eligible for thrombolysis/thrombectomy therapies. However, the narrow time windows of thrombolysis/thrombectomy, coupled with the risk of hemorrhagic transformation, as well as the lack of highly effective and safe medications, continue to present big challenges in the acute treatment and long-term recovery of IS. In the past 3 years, several excellent articles have reviewed pathophysiology of IS and therapeutic medicines for the treatment of IS based on the pathophysiology. Regretfully, there is no comprehensive overview to summarize all categories of anti-IS drugs/agents designed and synthesized based on molecular mechanisms of IS pathophysiology. From medicinal chemistry view of point, this article reviews a multitude of anti-IS drugs/agents, including small molecule compounds, natural products, peptides, and others, which have been developed based on the molecular mechanism of IS pathophysiology, such as excitotoxicity, oxidative/nitrosative stresses, cell death pathways, and neuroinflammation, and so forth. In addition, several emerging medicines and strategies, including nanomedicines, stem cell therapy and noncoding RNAs, which recently appeared for the treatment of IS, are shortly introduced. Finally, the perspectives on the associated challenges and future directions of anti-IS drugs/agents are briefly provided to move the field forward.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"975-1012"},"PeriodicalIF":13.3,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chui-Yan Ma, Yuqing Zhai, Chung Tony Li, Jie Liu, Xiang Xu, Hao Chen, Hung-Fat Tse, Qizhou Lian
{"title":"Translating mesenchymal stem cell and their exosome research into GMP compliant advanced therapy products: Promises, problems and prospects","authors":"Chui-Yan Ma, Yuqing Zhai, Chung Tony Li, Jie Liu, Xiang Xu, Hao Chen, Hung-Fat Tse, Qizhou Lian","doi":"10.1002/med.22002","DOIUrl":"10.1002/med.22002","url":null,"abstract":"<p>Mesenchymal stem cells (MSCs) are one of the few stem cell types used in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair, due to their unique paracrine capacity, multiple differentiation potential, active components in exosomes, and effective mitochondria donation. At present, MSCs derived from tissues such as bone marrow and umbilical cord are widely applied in preclinical and clinical studies. Nevertheless, there remain challenges to the maintenance of consistently good quality MSCs derived from different donors or tissues, directly impacting their application as advanced therapy products. In this review, we discuss the promises, problems, and prospects associated with translation of MSC research into a pharmaceutical product. We review the hurdles encountered in translation of MSCs and MSC–exosomes from the research bench to an advanced therapy product compliant with good manufacturing practice (GMP). These difficulties include how to set up GMP-compliant protocols, what factors affect raw material selection, cell expansion to product formulation, establishment of quality control (QC) parameters, and quality assurance to comply with GMP standards. To avoid human error and reduce the risk of contamination, an automatic, closed system that allows real-time monitoring of QC should be considered. We also highlight potential advantages of pluripotent stem cells as an alternative source for MSC and exosomes generation and manufacture.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"919-938"},"PeriodicalIF":13.3,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Njemuwa Nwaji, Juyong Gwak, My-Chi Nguyen, Huu-Quang Nguyen, Hyojin Kang, Youngeun Choi, Youngmi Kim, Hongxia Chen, Jaebeom Lee
{"title":"Emerging potentials of Fe-based nanomaterials for chiral sensing and imaging","authors":"Njemuwa Nwaji, Juyong Gwak, My-Chi Nguyen, Huu-Quang Nguyen, Hyojin Kang, Youngeun Choi, Youngmi Kim, Hongxia Chen, Jaebeom Lee","doi":"10.1002/med.22003","DOIUrl":"10.1002/med.22003","url":null,"abstract":"<p>Fe-based nanostructures have possessed promising properties that make it suitable for chiral sensing and imaging applications owing to their ultra-small size, non-toxicity, biocompatibility, excellent photostability, tunable fluorescence, and water solubility. This review summarizes the recent research progress in the field of Fe-based nanostructures and places special emphases on their applications in chiral sensing and imaging. The synthetic strategies to prepare the targeted Fe-based structures were also introduced. The chiral sensing and imaging applications of the nanostructures are discussed in details.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 3","pages":"897-918"},"PeriodicalIF":13.3,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138574527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artemisinins: Promising drug candidates for the treatment of autoimmune diseases","authors":"Xu Gao, Xian Lin, Qingwen Wang, Jian Chen","doi":"10.1002/med.22001","DOIUrl":"10.1002/med.22001","url":null,"abstract":"<p>Autoimmune diseases are characterized by the immune system's attack on one's own tissues which are highly diverse and diseases differ in severity, causing damage in virtually all human systems including connective tissue (e.g., rheumatoid arthritis), neurological system (e.g., multiple sclerosis) and digestive system (e.g., inflammatory bowel disease). Historically, treatments normally include pain-killing medication, anti-inflammatory drugs, corticosteroids, and immunosuppressant drugs. However, given the above characteristics, treatment of autoimmune diseases has always been a challenge. Artemisinin is a natural sesquiterpene lactone initially extracted and separated from Chinese medicine <i>Artemisia annua</i> L., which has a long history of curing malaria. Artemisinin's derivatives such as artesunate, dihydroartemisinin, artemether, artemisitene, and so forth, are a family of artemisinins with antimalarial activity. Over the past decades, accumulating evidence have indicated the promising therapeutic potential of artemisinins in autoimmune diseases. Herein, we systematically summarized the research regarding the immunoregulatory properties of artemisinins including artemisinin and its derivatives, discussing their potential therapeutic viability toward major autoimmune diseases and the underlying mechanisms. This review will provide new directions for basic research and clinical translational medicine of artemisinins.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 2","pages":"867-891"},"PeriodicalIF":13.3,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LSD1 in drug discovery: From biological function to clinical application","authors":"Hui-Min Liu, Ying Zhou, He-Xiang Chen, Jiang-Wan Wu, Shi-Kun Ji, Liang Shen, Shao-Peng Wang, Hong-Min Liu, Ying Liu, Xing-Jie Dai, Yi-Chao Zheng","doi":"10.1002/med.22000","DOIUrl":"10.1002/med.22000","url":null,"abstract":"<p>Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 2","pages":"833-866"},"PeriodicalIF":13.3,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Progress in RAS-targeted therapeutic strategies: From small molecule inhibitors to proteolysis targeting chimeras","authors":"Xinchen Lu, Jinmei Jin, Ye Wu, Xiaoxia Liu, Xiaohui Liang, Jiayi Lin, Qingyan Sun, Jiangjiang Qin, Weidong Zhang, Xin Luan","doi":"10.1002/med.21993","DOIUrl":"10.1002/med.21993","url":null,"abstract":"<p>As a widely considerable target in chemical biology and pharmacological research, rat sarcoma (RAS) gene mutations play a critical driving factor in several fatal cancers. Despite the great progress of RAS subtype-specific inhibitors, rapid acquired drug resistance could limit their further clinical applications. Proteolysis targeting chimera (PROTAC) has emerged as a powerful tool to handle “undruggable” targets and exhibited significant therapeutic benefit for the combat of drug resistance. Owing to unique molecular mechanism and binding kinetics, PROTAC is expected to become a feasible strategy to break the bottleneck of classical RAS inhibitors. This review aims to discuss the current advances of RAS inhibitors and especially focus on PROTAC strategy targeting RAS mutations and their downstream effectors for relevant cancer treatment.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 2","pages":"812-832"},"PeriodicalIF":13.3,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138439962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Zheng, Yuke Li, Mao Li, Rujing Wang, Yuhong Jiang, Mengnan Zhao, Jun Lu, Rui Li, Xiaofang Li, Sanjun Shi
{"title":"COVID-19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms","authors":"Yu Zheng, Yuke Li, Mao Li, Rujing Wang, Yuhong Jiang, Mengnan Zhao, Jun Lu, Rui Li, Xiaofang Li, Sanjun Shi","doi":"10.1002/med.21997","DOIUrl":"10.1002/med.21997","url":null,"abstract":"<p>As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to wreak havoc worldwide, the “Cytokine Storm” (CS, also known as the inflammatory storm) or Cytokine Release Syndrome has reemerged in the public consciousness. CS is a significant contributor to the deterioration of infected individuals. Therefore, CS control is of great significance for the treatment of critically ill patients and the reduction of mortality rates. With the occurrence of variants, concerns regarding the efficacy of vaccines and antiviral drugs with a broad spectrum have grown. We should make an effort to modernize treatment strategies to address the challenges posed by mutations. Thus, in addition to the requirement for additional clinical data to monitor the long-term effects of vaccines and broad-spectrum antiviral drugs, we can use CS as an entry point and therapeutic target to alleviate the severity of the disease in patients. To effectively combat the mutation, new technologies for neutralizing or controlling CS must be developed. In recent years, nanotechnology has been widely applied in the biomedical field, opening up a plethora of opportunities for CS. Here, we put forward the view of cytokine storm as a therapeutic target can be used to treat critically ill patients by expounding the relationship between coronavirus disease 2019 (COVID-19) and CS and the mechanisms associated with CS. We pay special attention to the representative strategies of nanomaterials in current neutral and CS research, as well as their potential chemical design and principles. We hope that the nanostrategies described in this review provide attractive treatment options for severe and critical COVID-19 caused by CS.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 2","pages":"738-811"},"PeriodicalIF":13.3,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138289886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qineng Gong, Haojie Wang, Mi Zhou, Lu Zhou, Renxiao Wang, Yan Li
{"title":"B-cell lymphoma-2 family proteins in the crosshairs: Small molecule inhibitors and activators for cancer therapy","authors":"Qineng Gong, Haojie Wang, Mi Zhou, Lu Zhou, Renxiao Wang, Yan Li","doi":"10.1002/med.21999","DOIUrl":"10.1002/med.21999","url":null,"abstract":"<p>The B-cell lymphoma-2 (BCL-2) family of proteins plays a crucial role in the regulation of apoptosis, offering a dual mechanism for its control. Numerous studies have established a strong association between gene disorders of these proteins and the proliferation of diverse cancer cell types. Consequently, the identification and development of drugs targeting BCL-2 family proteins have emerged as a prominent area in antitumor therapy. Over the last two decades, several small-molecules have been designed to modulate the protein–protein interactions between anti- and proapoptotic BCL-2 proteins, effectively suppressing tumor growth and metastasis in vivo. The primary focus of research has been on developing BCL-2 homology 3 (BH3) mimetics to target antiapoptotic BCL-2 proteins, thereby competitively releasing proapoptotic BCL-2 proteins and restoring the blocked intrinsic apoptotic program. Additionally, for proapoptotic BCL-2 proteins, exogenous small molecules have been explored to activate cell apoptosis by directly interacting with executioner proteins such as BCL-2-associated X protein (BAX) or BCL-2 homologous antagonist/killer protein (BAK). In this comprehensive review, we summarize the inhibitors and activators (sensitizers) of BCL-2 family proteins developed over the past decades, highlighting their discovery, optimization, preclinical and clinical status, and providing an overall landscape of drug development targeting these proteins for therapeutic purposes.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 2","pages":"707-737"},"PeriodicalIF":13.3,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naga Rajiv Lakkaniga, Zhengyu Wang, Yao Xiao, Anupreet Kharbanda, Li Lan, Hong-yu Li
{"title":"Revisiting Aurora Kinase B: A promising therapeutic target for cancer therapy","authors":"Naga Rajiv Lakkaniga, Zhengyu Wang, Yao Xiao, Anupreet Kharbanda, Li Lan, Hong-yu Li","doi":"10.1002/med.21994","DOIUrl":"10.1002/med.21994","url":null,"abstract":"<p>Cancer continues to be a major health concern globally, although the advent of targeted therapy has revolutionized treatment options. Aurora Kinase B is a serine-threonine kinase that has been explored as an oncology therapeutic target for more than two decades. Aurora Kinase B inhibitors show promising biological results in in-vitro and in-vivo experiments. However, there are no inhibitors approved yet for clinical use, primarily because of the side effects associated with Aurora B inhibitors. Several studies demonstrate that Aurora B inhibitors show excellent synergy with various chemotherapeutic agents, radiation therapy, and targeted therapies. This makes it an excellent choice as an adjuvant therapy to first-line therapies, which greatly improves the therapeutic window and side effect profile. Recent studies indicate the role of Aurora B in some deadly cancers with limited therapeutic options, like triple-negative breast cancer and glioblastoma. Herein, we review the latest developments in Aurora Kinase B targeted research, with emphasis on its potential as an adjuvant therapy and its role in some of the most difficult-to-treat cancers.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 2","pages":"686-706"},"PeriodicalIF":13.3,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}