Medicinal Research Reviews最新文献_第7页

Front Cover Image, Volume 44, Issue 4 封面图片，第 44 卷第 4 期

IF 13.3 1区医学

Medicinal Research Reviews Pub Date : 2024-06-08 DOI: 10.1002/med.22063

Li Ren, Tiehua Zhang, Jie Zhang

引用次数: 0

The antisickling agent, 5-hydroxymethyl-2-furfural: Other potential pharmacological applications 抗ickling剂，5-羟甲基-2-糠醛：其他潜在的药理应用。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-06-06 DOI: 10.1002/med.22062

Piyusha P. Pagare, Mina McGinn, Mohini S. Ghatge, Vibha Shekhar, Rana T. Alhashimi, B. Daniel Pierce, Osheiza Abdulmalik, Yan Zhang, Martin K. Safo

{"title":"The antisickling agent, 5-hydroxymethyl-2-furfural: Other potential pharmacological applications","authors":"Piyusha P. Pagare, Mina McGinn, Mohini S. Ghatge, Vibha Shekhar, Rana T. Alhashimi, B. Daniel Pierce, Osheiza Abdulmalik, Yan Zhang, Martin K. Safo","doi":"10.1002/med.22062","DOIUrl":"10.1002/med.22062","url":null,"abstract":"For the last two decades, the aromatic aldehyde 5-hydroxymethyl-furfural (5-HMF) has been the subject of several investigations for its pharmacologic potential. In 2004, the Safo group reported that 5-HMF has potent antisickling activity by targeting and ameliorating the primary pathophysiology of hypoxia-induced sickling of erythrocytes (red blood cells [RBC]). Following the encouraging outcome of the preclinical and phase I/II clinical studies of 5-HMF for the treatment of sickle cell disease (SCD), there have been multiple studies suggesting 5-HMF has several other biological or pharmacologic activities, including anti-allergic, antioxidant, anti-hypoxic, anti-ischemic, cognitive improvement, anti-tyrosinase, anti-proliferation, cytoprotective, and anti-inflammatory activities. The wide range of its effects makes 5-HMF a potential candidate for treating a variety of diseases including cognitive disorders, gout, allergic disorders, anemia, hypoxia, cancers, ischemia, hemorrhagic shock, liver fibrosis, and oxidative injury. Several of these therapeutic claims are currently under investigation and, while promising, vary in terms of the strength of their evidence. This review presents the research regarding the therapeutic potential of 5-HMF in addition to its sources, physicochemical properties, safety, absorption, distribution, metabolism, and excretion (ADME) profiles.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2707-2729"},"PeriodicalIF":10.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Advances in drug design and therapeutic potential of selective or multitarget 5-HT1A receptor ligands 选择性或多靶点 5-HT1A 受体配体的药物设计进展和治疗潜力。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-05-29 DOI: 10.1002/med.22049

Gianfabio Giorgioni, Alessandro Bonifazi, Luca Botticelli, Carlo Cifani, Federica Matteucci, Emanuela Micioni Di Bonaventura, Maria Vittoria Micioni Di Bonaventura, Mario Giannella, Alessandro Piergentili, Alessia Piergentili, Wilma Quaglia, Fabio Del Bello

{"title":"Advances in drug design and therapeutic potential of selective or multitarget 5-HT1A receptor ligands","authors":"Gianfabio Giorgioni, Alessandro Bonifazi, Luca Botticelli, Carlo Cifani, Federica Matteucci, Emanuela Micioni Di Bonaventura, Maria Vittoria Micioni Di Bonaventura, Mario Giannella, Alessandro Piergentili, Alessia Piergentili, Wilma Quaglia, Fabio Del Bello","doi":"10.1002/med.22049","DOIUrl":"10.1002/med.22049","url":null,"abstract":"5-HT1A receptor (5-HT1A-R) is a serotoninergic G-protein coupled receptor subtype which contributes to several physiological processes in both central nervous system and periphery. Despite being the first 5-HT-R identified, cloned and studied, it still represents a very attractive target in drug discovery and continues to be the focus of a myriad of drug discovery campaigns due to its involvement in numerous neuropsychiatric disorders. The structure-activity relationship studies (SAR) performed over the last years have been devoted to three main goals: (i) design and synthesis of 5-HT1A-R selective/preferential ligands; (ii) identification of 5-HT1A-R biased agonists, differentiating pre- versus post-synaptic agonism and signaling cellular mechanisms; (iii) development of multitarget compounds endowed with well-defined poly-pharmacological profiles targeting 5-HT1A-R along with other serotonin receptors, serotonin transporter (SERT), D2-like receptors and/or enzymes, such as acetylcholinesterase and phosphodiesterase, as a promising strategy for the management of complex psychiatric and neurodegenerative disorders. In this review, medicinal chemistry aspects of ligands acting as selective/preferential or multitarget 5-HT1A-R agonists and antagonists belonging to different chemotypes and developed in the last 7 years (2017–2023) have been discussed. The development of chemical and pharmacological 5-HT1A-R tools for molecular imaging have also been described. Finally, the pharmacological interest of 5-HT1A-R and the therapeutic potential of ligands targeting this receptor have been considered.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2640-2706"},"PeriodicalIF":10.9,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160822","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}

引用次数: 0

Counter-intuitive discovery in the formulation of poorly water-soluble drugs: Amorphous small-molecule gels 弱水溶性药物制剂中的反直觉发现：无定形小分子凝胶。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-05-28 DOI: 10.1002/med.22060

Yecheng Shu, Peixu Zhao, Xin Li, Xianbao Shi, Qiang Fu

引用次数: 0

Rethinking therapeutic strategies of dual-target drugs: An update on pharmacological small-molecule compounds in cancer 重新思考双靶点药物的治疗策略：癌症药理小分子化合物的最新进展。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-05-20 DOI: 10.1002/med.22057

Yiren Yang, Yi Mou, Lin-Xi Wan, Shiou Zhu, Guan Wang, Huiyuan Gao, Bo Liu

{"title":"Rethinking therapeutic strategies of dual-target drugs: An update on pharmacological small-molecule compounds in cancer","authors":"Yiren Yang, Yi Mou, Lin-Xi Wan, Shiou Zhu, Guan Wang, Huiyuan Gao, Bo Liu","doi":"10.1002/med.22057","DOIUrl":"10.1002/med.22057","url":null,"abstract":"Oncogenes and tumor suppressors are well-known to orchestrate several signaling cascades, regulate extracellular and intracellular stimuli, and ultimately control the fate of cancer cells. Accumulating evidence has recently revealed that perturbation of these key modulators by mutations or abnormal protein expressions are closely associated with drug resistance in cancer therapy; however, the inherent drug resistance or compensatory mechanism remains to be clarified for targeted drug discovery. Thus, dual-target drug development has been widely reported to be a promising therapeutic strategy for improving drug efficiency or overcoming resistance mechanisms. In this review, we provide an overview of the therapeutic strategies of dual-target drugs, especially focusing on pharmacological small-molecule compounds in cancer, including small molecules targeting mutation resistance, compensatory mechanisms, synthetic lethality, synergistic effects, and other new emerging strategies. Together, these therapeutic strategies of dual-target drugs would shed light on discovering more novel candidate small-molecule drugs for the future cancer treatment.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2600-2623"},"PeriodicalIF":10.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070006","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}

引用次数: 0

Bivalent and bitopic ligands of the opioid receptors: The prospects of a dual approach 阿片受体的二价配体和二价配体：双重方法的前景。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-05-15 DOI: 10.1002/med.22050

Marie Emilie Hovah, Ulrike Holzgrabe

{"title":"Bivalent and bitopic ligands of the opioid receptors: The prospects of a dual approach","authors":"Marie Emilie Hovah, Ulrike Holzgrabe","doi":"10.1002/med.22050","DOIUrl":"10.1002/med.22050","url":null,"abstract":"Opioid receptors belonging to the class A G-protein coupled receptors (GPCRs) are the targets of choice in the treatment of acute and chronic pain. However, their on-target side effects such as respiratory depression, tolerance and addiction have led to the advent of the ‘opioid crisis’. In the search for safer analgesics, bivalent and more recently, bitopic ligands have emerged as valuable tool compounds to probe these receptors. The activity of bivalent and bitopic ligands rely greatly on the allosteric nature of the GPCRs. Bivalent ligands consist of two pharmacophores, each binding to the individual orthosteric binding site (OBS) of the monomers within a dimer. Bitopic or dualsteric ligands bridge the gap between the OBS and the spatially distinct, less conserved allosteric binding site (ABS) through the simultaneous occupation of these two sites. Bivalent and bitopic ligands stabilize distinct conformations of the receptors which ultimately translates into unique signalling and pharmacological profiles. Some of the interesting properties shown by these ligands include improved affinity and/or efficacy, subtype and/or functional selectivity and reduced side effects. This review aims at providing an overview of some of the bivalent and bitopic ligands of the opioid receptors and, their pharmacology in the hope of inspiring the design and discovery of the next generation of opioid analgesics.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2545-2599"},"PeriodicalIF":10.9,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel 瞬态受体电位典范 3 离子通道的病理生理学意义和调制。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-05-07 DOI: 10.1002/med.22048

Vijay K. Boda, Nelufar Yasmen, Jianxiong Jiang, Wei Li

{"title":"Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel","authors":"Vijay K. Boda, Nelufar Yasmen, Jianxiong Jiang, Wei Li","doi":"10.1002/med.22048","DOIUrl":"10.1002/med.22048","url":null,"abstract":"Transient receptor potential canonical 3 (TRPC3) protein belongs to the TRP family of nonselective cation channels. Its activation occurs by signaling through a G protein-coupled receptor (GPCR) and a phospholipase C-dependent (PLC) pathway. Perturbations in the expression of TRPC3 are associated with a plethora of pathophysiological conditions responsible for disorders of the cardiovascular, immune, and central nervous systems. The recently solved cryo-EM structure of TRPC3 provides detailed inputs about the underlying mechanistic aspects of the channel, which in turn enables more efficient ways of designing small-molecule modulators. Pharmacologically targeting TRPC3 in animal models has demonstrated great efficacy in treating diseases including cancers, neurological disorders, and cardiovascular diseases. Despite extensive scientific evidence supporting some strong correlations between the expression and activity of TRPC3 and various pathophysiological conditions, therapeutic strategies based on its pharmacological modulations have not led to clinical trials. The development of small-molecule TRPC3 modulators with high safety, sufficient brain penetration, and acceptable drug-like profiles remains in progress. Determining the pathological mechanisms for TRPC3 involvement in human diseases and understanding the requirements for a drug-like TRPC3 modulator will be valuable in advancing small-molecule therapeutics to future clinical trials. In this review, we provide an overview of the origin and activation mechanism of TRPC3 channels, diseases associated with irregularities in their expression, and new development in small-molecule modulators as potential therapeutic interventions for treating TRPC3 channelopathies.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2510-2544"},"PeriodicalIF":10.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875362","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}

引用次数: 0

Targeting lysosomal quality control as a therapeutic strategy against aging and diseases 将溶酶体质量控制作为抗衰老和疾病的治疗策略。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-05-06 DOI: 10.1002/med.22047

Yuchen He, Yishu Fan, Xenab Ahmadpoor, Yumin Wang, Zhong Alan Li, Weihong Zhu, Hang Lin

{"title":"Targeting lysosomal quality control as a therapeutic strategy against aging and diseases","authors":"Yuchen He, Yishu Fan, Xenab Ahmadpoor, Yumin Wang, Zhong Alan Li, Weihong Zhu, Hang Lin","doi":"10.1002/med.22047","DOIUrl":"10.1002/med.22047","url":null,"abstract":"Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2472-2509"},"PeriodicalIF":10.9,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Engineering peptide drug therapeutics through chemical conjugation and implication in clinics 通过化学共轭技术开发多肽药物疗法及其在临床中的应用

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-05-05 DOI: 10.1002/med.22046

Syed Faheem Askari Rizvi, Haixia Zhang, Quan Fang

{"title":"Engineering peptide drug therapeutics through chemical conjugation and implication in clinics","authors":"Syed Faheem Askari Rizvi, Haixia Zhang, Quan Fang","doi":"10.1002/med.22046","DOIUrl":"10.1002/med.22046","url":null,"abstract":"The development of peptide drugs has made tremendous progress in the past few decades because of the advancements in modification chemistry and analytical technologies. The novel-designed peptide drugs have been modified through various biochemical methods with improved diagnostic, therapeutic, and drug-delivery strategies. Researchers found it a helping hand to overcome the inherent limitations of peptides and bring continued advancements in their applications. Furthermore, the emergence of peptide-drug conjugates (PDCs)—utilizes target-oriented peptide moieties as a vehicle for cytotoxic payloads via conjugation with cleavable chemical agents, resulting in the key foundation of the new era of targeted peptide drugs. This review summarizes the various classifications of peptide drugs, suitable chemical modification strategies to improve the ADME (adsorption, distribution, metabolism, and excretion) features of peptide drugs, and recent (2015–early 2024) progress/achievements in peptide-based drug delivery systems as well as their fruitful implication in preclinical and clinical studies. Furthermore, we also summarized the brief description of other types of PDCs, including peptide-MOF conjugates and peptide-UCNP conjugates. The principal aim is to provide scattered and diversified knowledge in one place and to help researchers understand the pinching knots in the science of PDC development and progress toward a bright future of novel peptide drugs.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2420-2471"},"PeriodicalIF":10.9,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829799","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}

引用次数: 0

Innovative pathological network-based multitarget approaches for Alzheimer's disease treatment 基于病理网络的多靶点阿尔茨海默病治疗创新方法

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-04-28 DOI: 10.1002/med.22045

Paloma Mayo, Jorge Pascual, Enrique Crisman, Cristina Domínguez, Manuela G. López, Rafael León

{"title":"Innovative pathological network-based multitarget approaches for Alzheimer's disease treatment","authors":"Paloma Mayo, Jorge Pascual, Enrique Crisman, Cristina Domínguez, Manuela G. López, Rafael León","doi":"10.1002/med.22045","DOIUrl":"10.1002/med.22045","url":null,"abstract":"Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is a major health threat globally. Its prevalence is forecasted to exponentially increase during the next 30 years due to the global aging population. Currently, approved drugs are merely symptomatic, being ineffective in delaying or blocking the relentless disease advance. Intensive AD research describes this disease as a highly complex multifactorial disease. Disclosure of novel pathological pathways and their interconnections has had a major impact on medicinal chemistry drug development for AD over the last two decades. The complex network of pathological events involved in the onset of the disease has prompted the development of multitarget drugs. These chemical entities combine pharmacological activities toward two or more drug targets of interest. These multitarget-directed ligands are proposed to modify different nodes in the pathological network aiming to delay or even stop disease progression. Here, we review the multitarget drug development strategy for AD during the last decade.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":"44 6","pages":"2367-2419"},"PeriodicalIF":10.9,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med.22045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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