Medicinal Research Reviews最新文献

Unleashing the Power of Covalent Drugs for Protein Degradation. 释放共价药物对蛋白质降解的作用。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-01-21 DOI: 10.1002/med.22101

Meng-Jie Fu, Hang Jin, Shao-Peng Wang, Liang Shen, Hong-Min Liu, Ying Liu, Yi-Chao Zheng, Xing-Jie Dai

{"title":"Unleashing the Power of Covalent Drugs for Protein Degradation.","authors":"Meng-Jie Fu, Hang Jin, Shao-Peng Wang, Liang Shen, Hong-Min Liu, Ying Liu, Yi-Chao Zheng, Xing-Jie Dai","doi":"10.1002/med.22101","DOIUrl":"https://doi.org/10.1002/med.22101","url":null,"abstract":"Targeted protein degradation (TPD) has emerged as a significant therapeutic approach for a variety of diseases, including cancer. Advances in TPD techniques, such as molecular glue (MG) and lysosome-dependent strategies, have shown substantial progress since the inception of the first PROTAC in 2001. The PROTAC methodology represents the forefront of TPD technology, with ongoing evaluation in more than 20 clinical trials for the treatment of diverse medical conditions. Two prominent PROTACs, ARV-471 and ARV-110, are currently undergoing phase III and II clinical trials, respectively. Traditional PROTACs are encountering obstacles such as limited binding affinity and a restricted range of E3 ligase ligands for facilitating the protein of interest (POI) degradation. Covalent medicines offer the potential to enhance PROTAC efficacy by enabling the targeting of previously considered \"undruggable\" shallow binding sites. Strategic alterations allow PROTAC to establish covalent connections with particular target proteins, including Kirsten rat sarcoma viral oncogene homolog (KRAS), Bruton's tyrosine kinase (BTK), epidermal growth factor receptor (EGFR), as well as E3 ligases such as DDB1 and CUL4 associated factor 16 (DCAF16) and Kelch-like ECH-associated protein 1 (Keap1). The concept of covalent degradation has also been utilized in various new forms of degraders, including covalent molecule glue (MG), in-cell click-formed proteolysis targeting chimera (CLIPTAC), HaloPROTAC, lysosome-targeting chimera (LYTAC) and GlueTAC. This review focuses on recent advancements in covalent degraders beyond covalent PROTACs and examines obstacles and future directions pertinent to this field.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997127","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

Proteomics: An In-Depth Review on Recent Technical Advances and Their Applications in Biomedicine.

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-01-09 DOI: 10.1002/med.22098

Jing Liang, Jundan Tian, Huadong Zhang, Hua Li, Lixia Chen

{"title":"Proteomics: An In-Depth Review on Recent Technical Advances and Their Applications in Biomedicine.","authors":"Jing Liang, Jundan Tian, Huadong Zhang, Hua Li, Lixia Chen","doi":"10.1002/med.22098","DOIUrl":"https://doi.org/10.1002/med.22098","url":null,"abstract":"Proteins hold pivotal importance since many diseases manifest changes in protein activity. Proteomics techniques provide a comprehensive exploration of protein structure, abundance, and function in biological samples, enabling the holistic characterization of overall changes in organisms. Nowadays, the breadth of emerging methodologies in proteomics is unprecedentedly vast, with constant optimization of technologies in sample processing, data collection, data analysis, and its scope of application is steadily transitioning from the bench to the clinic. Here, we offer an insightful review of the technical developments in proteomics and its applications in biomedicine over the past 5 years. We focus on its profound contributions in profiling disease spectra, discovering new biomarkers, identifying promising drug targets, deciphering alterations in protein conformation, and unearthing protein-protein interactions. Moreover, we summarize the cutting-edge technologies and potential breakthroughs in the proteomics pipeline and provide the principal challenges in proteomics. Based on these, we aspire to broaden the applicability of proteomics and inspire researchers to enhance our understanding of complex biological systems by utilizing such techniques.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941988","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

The Current Progress in the Quest for Vaccines Against the Semliki Forest Virus Complex. 塞姆利基森林病毒复合体疫苗研究的最新进展

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-01-05 DOI: 10.1002/med.22097

Dorothy Hui Juan Cheong, Bowen Yi, Yi Hao Wong, Justin Jang Hann Chu

{"title":"The Current Progress in the Quest for Vaccines Against the Semliki Forest Virus Complex.","authors":"Dorothy Hui Juan Cheong, Bowen Yi, Yi Hao Wong, Justin Jang Hann Chu","doi":"10.1002/med.22097","DOIUrl":"https://doi.org/10.1002/med.22097","url":null,"abstract":"The Semliki Forest virus (SFV) complex comprises of arboviruses that are transmitted by arthropod vectors and cause acute febrile illness in humans. In the last seven decades, re-emergence of these viruses has resulted in numerous outbreaks globally, affecting regions including Africa, Americas, Asia, Europe and the Caribbean. These viruses are transmitted to humans by the bite of infected mosquitoes. Symptoms of infection include high fever, severe joint pain, skin rash, muscle pain and headache. Fatal cases were reported, and mortality rate increased during the epidemic of these viruses. There is therefore a need to control the spread of these emerging arboviruses. Given that vaccination is one of the most effective ways to protect populations against viral outbreaks, efforts have been made to develop and test potential vaccine candidates. However, there are still no licensed vaccines available against the medically important viruses in the SFV complex. This review first summarizes the current knowledge of the SFV complex disease pathogenesis. Next, seven strategies that have been applied in vaccine development against these viruses are reviewed, indicating the immune response and efficacies of these vaccine candidates in in vivo models of infection. Finally, the more promising candidates that have entered clinical trials are discussed and insights into the future development of vaccines for viruses of the SFV complex are given.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930145","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

Spatiotemporal Control Over Circadian Rhythms With Light.

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2025-01-05 DOI: 10.1002/med.22099

Dušan Kolarski, Wiktor Szymanski, Ben L Feringa

{"title":"Spatiotemporal Control Over Circadian Rhythms With Light.","authors":"Dušan Kolarski, Wiktor Szymanski, Ben L Feringa","doi":"10.1002/med.22099","DOIUrl":"https://doi.org/10.1002/med.22099","url":null,"abstract":"Circadian rhythms are endogenous biological oscillators that synchronize internal physiological processes and behaviors with external environmental changes, sustaining homeostasis and health. Disruption of circadian rhythms leads to numerous diseases, including cardiovascular and metabolic diseases, cancer, diabetes, and neurological disorders. Despite the potential to restore healthy rhythms in the organism, pharmacological chronotherapy lacks spatial and temporal resolution. Addressing this challenge, chrono-photopharmacology, the approach that employs small molecules with light-controlled activity, enables the modulation of circadian rhythms when and where needed. Two approaches-relying on irreversible and reversible drug activation-have been proposed for this purpose. These methodologies are based on photoremovable protecting groups and photoswitches, respectively. Designing photoresponsive bioactive molecules requires meticulous structural optimization to obtain the desired chemical and photophysical properties, and the design principles, detailed guidelines and challenges are summarized here. In this review, we also analyze all the known circadian modulators responsive to light and dissect the rationale following their construction and application to control circadian biology from the protein level to living organisms. Finally, we present the strength of a reversible approach in allowing the modulation of the circadian period and the phase.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930144","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

α-Synuclein in Parkinson's Disease: From Bench to Bedside.

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-20 DOI: 10.1002/med.22091

Gabriele Bellini, Vanessa D'Antongiovanni, Giovanni Palermo, Luca Antonioli, Matteo Fornai, Roberto Ceravolo, Nunzia Bernardini, Pascal Derkinderen, Carolina Pellegrini

{"title":"α-Synuclein in Parkinson's Disease: From Bench to Bedside.","authors":"Gabriele Bellini, Vanessa D'Antongiovanni, Giovanni Palermo, Luca Antonioli, Matteo Fornai, Roberto Ceravolo, Nunzia Bernardini, Pascal Derkinderen, Carolina Pellegrini","doi":"10.1002/med.22091","DOIUrl":"https://doi.org/10.1002/med.22091","url":null,"abstract":"α-Synuclein (α-syn), a pathological hallmark of PD, is emerging as a bridging element at the crossroads between neuro/immune-inflammatory responses and neurodegeneration in PD. Several evidence show that pathological α-syn accumulates in neuronal and non-neuronal cells (i.e., neurons, microglia, macrophages, skin cells, and intestinal cells) in central and peripheral tissues since the prodromal phase of the disease, contributing to brain pathology. Indeed, pathological α-syn deposition can promote neurogenic/immune-inflammatory responses that contribute to systemic and central neuroinflammation associated with PD. After providing an overview of the structure and functions of physiological α-syn as well as its pathological forms, we review current studies about the role of neuronal and non-neuronal α-syn at the crossroads between neuroinflammation and neurodegeneration in PD. In addition, we provide an overview of the correlation between the accumulation of α-syn in central and peripheral tissues and PD, related symptoms, and neuroinflammation. Special attention was paid to discussing whether targeting α-syn can represent a suitable therapeutical approach for PD.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862708","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

Advances in the Delivery, Activation and Therapeutics Applications of Bioorthogonal Prodrugs.

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-18 DOI: 10.1002/med.22095

Zhou Zhou, Yuanjun Sun, Jing Pang, Ya-Qiu Long

{"title":"Advances in the Delivery, Activation and Therapeutics Applications of Bioorthogonal Prodrugs.","authors":"Zhou Zhou, Yuanjun Sun, Jing Pang, Ya-Qiu Long","doi":"10.1002/med.22095","DOIUrl":"https://doi.org/10.1002/med.22095","url":null,"abstract":"Traditional prodrug strategies have been leveraged to overcome many inherent drawbacks of active native drugs in the drug research and development. However, endogenous stimuli such as specific microenvironment or enzymes are relied on to achieve the prodrug activation, resulting in unintended drug release and systemic toxicity. Alternatively, bioorthogonal cleavage reaction-enabled bioorthogonal prodrugs activation via exogenous triggers has emerged as a valuable approach, featuring spatiotemporally controlled drug release. Such bioorthogonal prodrug strategies would ensure targeted drug delivery and/or in situ generation, further circumventing systemic toxicity or premature elimination of active drugs. In recent years, metal-free bioorthogonal cleavage reactions with fast kinetics have boomed in the bioorthogonal prodrug design. Meanwhile, transition-metal-catalyzed and photocatalytic deprotection reactions have also been developed to trigger prodrug activation in biological systems. Besides traditional small molecule prodrugs, gasotransmitters have been successfully delivered to specific organelles or cells via bioorthogonal reactions, and nanosystems have been devised into bioorthogonal triggers as well. Herein, we present an overview of the latest advances in these bioorthogonally-uncaged prodrugs, focused on the delivery, activation and therapeutics applications.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845430","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

Comparison of Radionuclide Drug Conjugates With Boron Neutron Capture Therapy: An Overview of Targeted Charged Particle Radiation Therapy.

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-17 DOI: 10.1002/med.22093

Yingjun Zhang, Paolo Coghi, Zimo Ren, Narayan S Hosmane, Yinghuai Zhu

引用次数: 0

Front Cover Image, Volume 45, Issue 1

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-12-13 DOI: 10.1002/med.22094

Jinyi Wang, Tingting Zhou

引用次数: 0

β₃-Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta. β3-肾上腺素受体激动剂模拟宫内缺氧的生物效应：向药理人工胎盘迈出一大步。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-11-27 DOI: 10.1002/med.22092

Luca Filippi, Francesca Innocenti, Francesca Pascarella, Rosa Teresa Scaramuzzo, Riccardo Morganti, Paola Bagnoli, Maurizio Cammalleri, Massimo Dal Monte, Maura Calvani, Alessandro Pini

{"title":"β3-Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta.","authors":"Luca Filippi, Francesca Innocenti, Francesca Pascarella, Rosa Teresa Scaramuzzo, Riccardo Morganti, Paola Bagnoli, Maurizio Cammalleri, Massimo Dal Monte, Maura Calvani, Alessandro Pini","doi":"10.1002/med.22092","DOIUrl":"https://doi.org/10.1002/med.22092","url":null,"abstract":"At different stages of life, from embryonic to postnatal, varying oxygen concentrations modulate cellular gene expression by enhancing or repressing hypoxia-inducible transcription factors. During embryonic/fetal life, these genes encode proteins involved in adapting to a low-oxygen environment, including the induction of specific enzymes related to glycolytic metabolism, erythropoiesis, angiogenesis, and vasculogenesis. However, oxygen concentrations fluctuate during intrauterine life, enabling the induction of tissue-specific differentiation processes. Fetal well-being is thus closely linked to the physiological benefits of a dynamically hypoxic environment. Premature birth entails the precocious exposure of the immature fetus to a more oxygen-rich environment compared to the womb. As a result, preterm newborns face a condition of relative hyperoxia, which alters the postnatal development of organs and contributes to prematurity-related diseases. However, until recently, the molecular mechanism by which high oxygen tension alters normal fetal differentiation remained unclear. In this review, we discuss the research trajectory followed by our research group, which suggests that early exposure to a relatively hyperoxic environment may impair preterm neonates due to reduced expression of the β3-adrenoceptor. Additionally, we explore how these impairments could be prevented through the pharmacological stimulation of the remaining β3-adrenoceptors. Recent preclinical studies demonstrate that pharmacological stimulation of the β3-adrenoceptor can decouple exposure to hyperoxia from its harmful effects, offering a glimpse of the possibility to recreating the conditions typical of intrauterine life, even after premature birth.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737953","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

Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities. 从微环境动力学和分子洞察到生物标记分析和治疗模式，解密三阴性乳腺癌的全貌。

IF 10.9 1区医学

Medicinal Research Reviews Pub Date : 2024-10-24 DOI: 10.1002/med.22090

Harshita Tiwari, Swati Singh, Sonal Sharma, Priyamvada Gupta, Ashish Verma, Amrit Chattopadhaya, Brijesh Kumar, Sakshi Agarwal, Rajiv Kumar, Sanjeev Kumar Gupta, Vibhav Gautam

{"title":"Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities.","authors":"Harshita Tiwari, Swati Singh, Sonal Sharma, Priyamvada Gupta, Ashish Verma, Amrit Chattopadhaya, Brijesh Kumar, Sakshi Agarwal, Rajiv Kumar, Sanjeev Kumar Gupta, Vibhav Gautam","doi":"10.1002/med.22090","DOIUrl":"https://doi.org/10.1002/med.22090","url":null,"abstract":"Triple negative breast cancer (TNBC) displays a notable challenge in clinical oncology due to its invasive nature which is attributed to the absence of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor (HER-2). The heterogenous tumor microenvironment (TME) of TNBC is composed of diverse constituents that intricately interact to evade immune response and facilitate cancer progression and metastasis. Based on molecular gene expression, TNBC is classified into four molecular subtypes: basal-like (BL1 and BL2), luminal androgen receptor (LAR), immunomodulatory (IM), and mesenchymal. TNBC is an aggressive histological variant with adverse prognosis and poor therapeutic response. The lack of response in most of the TNBC patients could be attributed to the heterogeneity of the disease, highlighting the need for more effective treatments and reliable prognostic biomarkers. Targeting certain signaling pathways and their components has emerged as a promising therapeutic strategy for improving patient outcomes. In this review, we have summarized the interactions among various components of the dynamic TME in TNBC and discussed the classification of its molecular subtypes. Moreover, the purpose of this review is to compile and provide an overview of the most recent data about recently discovered novel TNBC biomarkers and targeted therapeutics that have proven successful in treating metastatic TNBC. The emergence of novel therapeutic strategies such as chemoimmunotherapy, chimeric antigen receptor (CAR)-T cells-based immunotherapy, phytometabolites-mediated natural therapy, photodynamic and photothermal approaches have made a significant positive impact and have paved the way for more effective interventions.","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491740","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