Pub Date : 2024-10-08DOI: 10.2174/0113894501312571240920070441
Chandrashekhar Sahu, Ram Kumar Sahu, Amit Roy
The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.
{"title":"A Review on Nanotechnologically Derived Phytomedicines for the Treatment of Hepatocellular Carcinoma: Recent Advances in Molecular Mechanism and Drug Targeting.","authors":"Chandrashekhar Sahu, Ram Kumar Sahu, Amit Roy","doi":"10.2174/0113894501312571240920070441","DOIUrl":"https://doi.org/10.2174/0113894501312571240920070441","url":null,"abstract":"<p><p>The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-08DOI: 10.2174/0113894501304747240823111337
Rakesh D Amrutkar, Mehul V Amesar, Lokesh B Chavan, Nilesh S Baviskar, Vaibhav B Bhamare
The family of proteins known as Bromodomain and Extra-Terminal (BET) proteins has become a key participant in the control of gene expression, having a significant impact on numerous physiological and pathological mechanisms. This review offers a thorough investigation of the BET protein family, clarifying its various roles in essential cellular processes and its connection to a variety of illnesses, from inflammatory disorders to cancer. The article explores the structural and functional features of BET proteins, emphasizing their special bromodomain modules that control chromatin dynamics by identifying acetylated histones. BET proteins' complex roles in the development of cardiovascular, neurodegenerative, and cancer diseases are carefully investigated, providing insight into possible treatment avenues. In addition, the review carefully examines the history and relevance of BET inhibitors, demonstrating their capacity to modify gene expression profiles and specifically target BET proteins. The encouraging outcomes of preclinical and clinical research highlight BET inhibitors' therapeutic potential across a range of disease contexts. The article summarizes the state of BET inhibitors today and makes predictions about the challenges and future directions of the field. This article provides insights into the changing field of BET protein-targeted interventions by discussing the potential of personalized medicine and combination therapies involving BET inhibitors. This thorough analysis combines many aspects of BET proteins, such as their physiological roles and their roles in pathophysiological conditions. As such, it is an invaluable tool for scientists and medical professionals who are trying to figure out how to treat patients by using this fascinating protein family.
Bromodomain and Extra-Terminal (BET) 蛋白家族已成为控制基因表达的关键参与者,对许多生理和病理机制产生了重大影响。这篇综述对 BET 蛋白家族进行了深入研究,阐明了它在重要细胞过程中的各种作用,以及它与从炎症性疾病到癌症等各种疾病的联系。文章探讨了 BET 蛋白的结构和功能特点,强调了其特殊的溴域模块,该模块通过识别乙酰化组蛋白来控制染色质动力学。文章仔细研究了 BET 蛋白在心血管疾病、神经退行性疾病和癌症发展过程中的复杂作用,为可能的治疗途径提供了启示。此外,综述还仔细研究了 BET 抑制剂的历史和相关性,展示了它们改变基因表达谱和特异性靶向 BET 蛋白的能力。临床前和临床研究取得的令人鼓舞的成果凸显了 BET 抑制剂在各种疾病中的治疗潜力。文章总结了 BET 抑制剂目前的发展状况,并预测了该领域面临的挑战和未来的发展方向。本文通过讨论个性化医疗和涉及 BET 抑制剂的联合疗法的潜力,深入探讨了不断变化的 BET 蛋白靶向干预领域。这篇详尽的分析结合了 BET 蛋白的许多方面,如其生理作用及其在病理生理条件下的作用。因此,对于那些试图找出如何利用这个迷人的蛋白家族来治疗病人的科学家和医学专家来说,这是一本非常有价值的工具书。
{"title":"Precision Targeting of BET Proteins - Navigating Disease Pathways, Inhibitor Insights, and Shaping Therapeutic Frontiers: A Comprehensive Review.","authors":"Rakesh D Amrutkar, Mehul V Amesar, Lokesh B Chavan, Nilesh S Baviskar, Vaibhav B Bhamare","doi":"10.2174/0113894501304747240823111337","DOIUrl":"https://doi.org/10.2174/0113894501304747240823111337","url":null,"abstract":"<p><p>The family of proteins known as Bromodomain and Extra-Terminal (BET) proteins has become a key participant in the control of gene expression, having a significant impact on numerous physiological and pathological mechanisms. This review offers a thorough investigation of the BET protein family, clarifying its various roles in essential cellular processes and its connection to a variety of illnesses, from inflammatory disorders to cancer. The article explores the structural and functional features of BET proteins, emphasizing their special bromodomain modules that control chromatin dynamics by identifying acetylated histones. BET proteins' complex roles in the development of cardiovascular, neurodegenerative, and cancer diseases are carefully investigated, providing insight into possible treatment avenues. In addition, the review carefully examines the history and relevance of BET inhibitors, demonstrating their capacity to modify gene expression profiles and specifically target BET proteins. The encouraging outcomes of preclinical and clinical research highlight BET inhibitors' therapeutic potential across a range of disease contexts. The article summarizes the state of BET inhibitors today and makes predictions about the challenges and future directions of the field. This article provides insights into the changing field of BET protein-targeted interventions by discussing the potential of personalized medicine and combination therapies involving BET inhibitors. This thorough analysis combines many aspects of BET proteins, such as their physiological roles and their roles in pathophysiological conditions. As such, it is an invaluable tool for scientists and medical professionals who are trying to figure out how to treat patients by using this fascinating protein family.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-07DOI: 10.2174/0113894501335877240926101134
Sadat Shafi, Mohammad Ahmed Khan, Javed Ahmad, Syed Arman Rabbani, Shailja Singh, Abul Kalam Najmi
Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells. This oncogenic transformation consequently results in elevated expression of glucose transporters in these cells. Moreover, various cancers exhibit abnormal transporter expression patterns compared to normal tissues. Recent investigations have underlined the significance of glucose transporters in regulating cancer cell survival, proliferation, and metastasis. Abnormal regulation of these transporters, which exhibit varying affinities for hexoses, could enable cancer cells to efficiently manage their energy supply, offering a crucial edge for proliferation. Exploiting the upregulated expression of glucose transporters, GLUTs, and Sodium Linked Glucose Transporters (SGLTs), could serve as a novel therapeutic intervention for anti-cancer drug discovery as well as provide a unique targeting approach for drug delivery to specific tumor tissues. This review aims to discussthe previous and emerging research on the expression of various types of glucose transporters in tumor tissues, the role of glucose transport inhibitors as a cancer therapy intervention as well as emerging GLUT/SGLT-mediated drug delivery strategies that can be therapeutically employed to target various cancers.
{"title":"Envisioning Glucose Transporters (GLUTs and SGLTs) as Novel Intervention against Cancer: Drug Discovery Perspective and Targeting Approach.","authors":"Sadat Shafi, Mohammad Ahmed Khan, Javed Ahmad, Syed Arman Rabbani, Shailja Singh, Abul Kalam Najmi","doi":"10.2174/0113894501335877240926101134","DOIUrl":"https://doi.org/10.2174/0113894501335877240926101134","url":null,"abstract":"<p><p>Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells. This oncogenic transformation consequently results in elevated expression of glucose transporters in these cells. Moreover, various cancers exhibit abnormal transporter expression patterns compared to normal tissues. Recent investigations have underlined the significance of glucose transporters in regulating cancer cell survival, proliferation, and metastasis. Abnormal regulation of these transporters, which exhibit varying affinities for hexoses, could enable cancer cells to efficiently manage their energy supply, offering a crucial edge for proliferation. Exploiting the upregulated expression of glucose transporters, GLUTs, and Sodium Linked Glucose Transporters (SGLTs), could serve as a novel therapeutic intervention for anti-cancer drug discovery as well as provide a unique targeting approach for drug delivery to specific tumor tissues. This review aims to discussthe previous and emerging research on the expression of various types of glucose transporters in tumor tissues, the role of glucose transport inhibitors as a cancer therapy intervention as well as emerging GLUT/SGLT-mediated drug delivery strategies that can be therapeutically employed to target various cancers.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.2174/0113894501328461240921062056
Yulu Chen, Qi Gao, Dan Wang, Xun Zou, Xiuming Li, Jing Ji, Bin Liu
This review provides a comprehensive overview of the recent advancements in research on ATF4 (Activating Transcription Factor 4) within the field of oncology. As a crucial transcription factor, ATF4 has garnered increasing attention for its role in cancer research. The review begins with an exploration of the regulatory mechanisms of ATF4, including its transcriptional control, post-translational modifications, and interactions with other transcription factors. It then highlights key research findings on ATF4's involvement in various aspects of tumor biology, such as cell proliferation, differentiation, apoptosis and survival, invasion and metastasis, and the tumor microenvironment. Furthermore, the review discusses the potential of targeting ATF4 as a novel therapeutic strategy for cancer treatment. It also explores how ATF4's interactions with existing anticancer drugs could inform the development of more effective therapeutic agents. By elucidating the role of ATF4 in tumor biology and its potential clinical applications, this review aims to provide new insights and strategies for cancer treatment.
{"title":"An Overview of Research Advances in Oncology Regarding the Transcription Factor ATF4.","authors":"Yulu Chen, Qi Gao, Dan Wang, Xun Zou, Xiuming Li, Jing Ji, Bin Liu","doi":"10.2174/0113894501328461240921062056","DOIUrl":"https://doi.org/10.2174/0113894501328461240921062056","url":null,"abstract":"<p><p>This review provides a comprehensive overview of the recent advancements in research on ATF4 (Activating Transcription Factor 4) within the field of oncology. As a crucial transcription factor, ATF4 has garnered increasing attention for its role in cancer research. The review begins with an exploration of the regulatory mechanisms of ATF4, including its transcriptional control, post-translational modifications, and interactions with other transcription factors. It then highlights key research findings on ATF4's involvement in various aspects of tumor biology, such as cell proliferation, differentiation, apoptosis and survival, invasion and metastasis, and the tumor microenvironment. Furthermore, the review discusses the potential of targeting ATF4 as a novel therapeutic strategy for cancer treatment. It also explores how ATF4's interactions with existing anticancer drugs could inform the development of more effective therapeutic agents. By elucidating the role of ATF4 in tumor biology and its potential clinical applications, this review aims to provide new insights and strategies for cancer treatment.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.2174/0113894501319817240919103802
Ritika Sharma, Avneet Kour, Hitesh Kumar Dewangan
Parkinson's disease (PD) is a complex neurological condition caused due to inheritance, environment, and behavior among various other parameters. The onset, diagnosis, course of therapy, and future of PD are thoroughly examined in this comprehensive review. This review also insights into pathogenic mechanisms of reactive microgliosis, Lewy bodies, and their functions in the evolution of PD. It addresses interaction complexity with genetic mutations, especially in genes such as UCH-L1, parkin, and α-synuclein, which illuminates changes in the manner dopaminergic cells handle proteins and use proteases. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy. This raises the improved outcomes and life quality for those with PD. Potential treatments for severe PD include new surgical methods like Deep Brain Stimulation (DBS). Further, exploration of non-motor manifestations, such as cognitive impairment, autonomic dysfunction, and others, is covered in this review article. These symptoms have a significant impact on patients' quality of life. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy.
{"title":"Enhancements in Parkinson's Disease Management: Leveraging Levodopa Optimization and Surgical Breakthroughs.","authors":"Ritika Sharma, Avneet Kour, Hitesh Kumar Dewangan","doi":"10.2174/0113894501319817240919103802","DOIUrl":"https://doi.org/10.2174/0113894501319817240919103802","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a complex neurological condition caused due to inheritance, environment, and behavior among various other parameters. The onset, diagnosis, course of therapy, and future of PD are thoroughly examined in this comprehensive review. This review also insights into pathogenic mechanisms of reactive microgliosis, Lewy bodies, and their functions in the evolution of PD. It addresses interaction complexity with genetic mutations, especially in genes such as UCH-L1, parkin, and α-synuclein, which illuminates changes in the manner dopaminergic cells handle proteins and use proteases. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy. This raises the improved outcomes and life quality for those with PD. Potential treatments for severe PD include new surgical methods like Deep Brain Stimulation (DBS). Further, exploration of non-motor manifestations, such as cognitive impairment, autonomic dysfunction, and others, is covered in this review article. These symptoms have a significant impact on patients' quality of life. One of the emerging therapeutic routes that are being investigated is neuroprotective medicines that aim to prevent the aggregation of α-synuclein and interventions that modify the progression of diseases. The review concludes by stressing the dynamic nature of PD research and the potential game-changing impact of precision medicines on current approaches to therapy.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.2174/0113894501324437240919064715
Ana Luísa Rodriguez Gini, Emilio Emilio João, Juliana Romano Lopes, Pamela Souza Tada Da Cunha, Angela Maria Arenas Velásquez, Marcia Aparecida Silva Graminha, Jean Leandro Dos Santos, Cauê Benito Scarim
The expression and release of cysteine proteases by Leishmania spp. and their virulence factors significantly influence the modulation of host immune responses and metabolism, rendering cysteine proteases intriguing targets for drug development. This review article explores the substantial role of cysteine protease B (CPB) in medicinal chemistry from 2001 to 2024, particularly concerning combatting Leishmania parasites. We delve into contemporary advancements and potential prospects associated with targeting cysteine proteases for therapeutic interventions against leishmaniasis, emphasizing drug discovery in this context. Computational analysis using the pkCSM tool assessed the physicochemical properties of compounds, providing valuable insights into their molecular characteristics and drug-like potential, enriching our understanding of the pharmacological profiles, and aiding rational inhibitor design. Our investigation highlights that while nonpeptidic compounds constitute the majority (69.2%, 36 compounds) of the dataset, peptidomimetic- based derivatives (30.8%, 16 compounds) also hold promise in medicinal chemistry. Evaluating the most promising compounds based on dissociation constant (Ki) and half maximal inhibitory concentration (IC50) values revealed notable potency, with 41.7% and 80.0% of nonpeptidic compounds exhibiting values < 1 μM, respectively. On the other hand, all peptidic compounds evaluated for Ki (43.8%) and IC50 (31.3%) obtained values < 1 μM, respectively. Further analysis identified specific compounds within both categories (nonpeptidic: 1, 2, and 4; peptidic: 48-52) as particularly promising, warranting deeper investigation into their structure-activity relationships. These findings underscore the diverse landscape of inhibitors in medicinal chemistry and highlight the potential of both nonpeptidic and peptide-based compounds as valuable assets in therapeutic development against leishmaniasis.
{"title":"Advances in Cysteine Protease B Inhibitors for Leishmaniasis Treatment.","authors":"Ana Luísa Rodriguez Gini, Emilio Emilio João, Juliana Romano Lopes, Pamela Souza Tada Da Cunha, Angela Maria Arenas Velásquez, Marcia Aparecida Silva Graminha, Jean Leandro Dos Santos, Cauê Benito Scarim","doi":"10.2174/0113894501324437240919064715","DOIUrl":"https://doi.org/10.2174/0113894501324437240919064715","url":null,"abstract":"<p><p>The expression and release of cysteine proteases by Leishmania spp. and their virulence factors significantly influence the modulation of host immune responses and metabolism, rendering cysteine proteases intriguing targets for drug development. This review article explores the substantial role of cysteine protease B (CPB) in medicinal chemistry from 2001 to 2024, particularly concerning combatting Leishmania parasites. We delve into contemporary advancements and potential prospects associated with targeting cysteine proteases for therapeutic interventions against leishmaniasis, emphasizing drug discovery in this context. Computational analysis using the pkCSM tool assessed the physicochemical properties of compounds, providing valuable insights into their molecular characteristics and drug-like potential, enriching our understanding of the pharmacological profiles, and aiding rational inhibitor design. Our investigation highlights that while nonpeptidic compounds constitute the majority (69.2%, 36 compounds) of the dataset, peptidomimetic- based derivatives (30.8%, 16 compounds) also hold promise in medicinal chemistry. Evaluating the most promising compounds based on dissociation constant (Ki) and half maximal inhibitory concentration (IC50) values revealed notable potency, with 41.7% and 80.0% of nonpeptidic compounds exhibiting values < 1 μM, respectively. On the other hand, all peptidic compounds evaluated for Ki (43.8%) and IC50 (31.3%) obtained values < 1 μM, respectively. Further analysis identified specific compounds within both categories (nonpeptidic: 1, 2, and 4; peptidic: 48-52) as particularly promising, warranting deeper investigation into their structure-activity relationships. These findings underscore the diverse landscape of inhibitors in medicinal chemistry and highlight the potential of both nonpeptidic and peptide-based compounds as valuable assets in therapeutic development against leishmaniasis.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.2174/0113894501320839240918110656
Maneesh Mohan, Ashi Mannan, Chirag Kakkar, Thakur Gurjeet Singh
Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.
{"title":"Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.","authors":"Maneesh Mohan, Ashi Mannan, Chirag Kakkar, Thakur Gurjeet Singh","doi":"10.2174/0113894501320839240918110656","DOIUrl":"https://doi.org/10.2174/0113894501320839240918110656","url":null,"abstract":"<p><p>Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SERCA2, a P-type ATPase located on the endoplasmic reticulum of cells, plays an important role in maintaining calcium balance within cells by transporting calcium from the cytoplasm to the endoplasmic reticulum against its concentration gradient. A multitude of studies have demonstrated that the expression of SERCA2 is abnormal in a wide variety of tumor cells. Consequently, research exploring compounds that target SERCA2 may offer a promising avenue for the development of novel anti-tumor drugs. This review has summarized the anti-tumor compounds targeting SERCA2, including thapsigargin, dihydroartemisinin, curcumin, galangin, etc. These compounds interact with SERCA2 on the endoplasmic reticulum membrane, disrupting intracellular calcium ion homeostasis, leading to tumor cell apoptosis, autophagy and cell cycle arrest, ultimately producing anti-tumor effects. Additionally, several potential research directions for compounds targeting SERCA2 as clinical anti-cancer drugs have been proposed in the review. In summary, SERCA2 is a promising anti-tumor target for drug discovery and development.
SERCA2 是位于细胞内质网上的一种 P 型 ATP 酶,通过逆浓度梯度将钙从细胞质输送到内质网,在维持细胞内的钙平衡方面发挥着重要作用。大量研究表明,在多种肿瘤细胞中,SERCA2 的表达都不正常。因此,探索以 SERCA2 为靶点的化合物的研究可能为开发新型抗肿瘤药物提供了一条前景广阔的途径。本综述总结了以 SERCA2 为靶点的抗肿瘤化合物,包括thapsigargin、双氢青蒿素、姜黄素、高良姜素等。这些化合物与内质网膜上的SERCA2相互作用,破坏细胞内钙离子平衡,导致肿瘤细胞凋亡、自噬和细胞周期停滞,最终产生抗肿瘤作用。此外,综述还提出了以 SERCA2 为靶点的化合物作为临床抗癌药物的几个潜在研究方向。总之,SERCA2 是一个很有前景的抗肿瘤药物发现和开发靶点。
{"title":"Targeting SERCA2 in Anti-Tumor Drug Discovery.","authors":"Wanqian Song, Qiuju Zhang, Zhiyong Cao, Guo Jing, Tiancheng Zhan, Yongkang Yuan, Ning Kang, Qiang Zhang","doi":"10.2174/0113894501325497240918042654","DOIUrl":"https://doi.org/10.2174/0113894501325497240918042654","url":null,"abstract":"<p><p>SERCA2, a P-type ATPase located on the endoplasmic reticulum of cells, plays an important role in maintaining calcium balance within cells by transporting calcium from the cytoplasm to the endoplasmic reticulum against its concentration gradient. A multitude of studies have demonstrated that the expression of SERCA2 is abnormal in a wide variety of tumor cells. Consequently, research exploring compounds that target SERCA2 may offer a promising avenue for the development of novel anti-tumor drugs. This review has summarized the anti-tumor compounds targeting SERCA2, including thapsigargin, dihydroartemisinin, curcumin, galangin, etc. These compounds interact with SERCA2 on the endoplasmic reticulum membrane, disrupting intracellular calcium ion homeostasis, leading to tumor cell apoptosis, autophagy and cell cycle arrest, ultimately producing anti-tumor effects. Additionally, several potential research directions for compounds targeting SERCA2 as clinical anti-cancer drugs have been proposed in the review. In summary, SERCA2 is a promising anti-tumor target for drug discovery and development.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.2174/0113894501330963240905083020
Gelany Aly Abdelkader, Jeong-Dong Kim
Background: Drug discovery is a complex and expensive procedure involving several timely and costly phases through which new potential pharmaceutical compounds must pass to get approved. One of these critical steps is the identification and optimization of lead compounds, which has been made more accessible by the introduction of computational methods, including deep learning (DL) techniques. Diverse DL model architectures have been put forward to learn the vast landscape of interaction between proteins and ligands and predict their affinity, helping in the identification of lead compounds.
Objective: This survey fills a gap in previous research by comprehensively analyzing the most commonly used datasets and discussing their quality and limitations. It also offers a comprehensive classification of the most recent DL methods in the context of protein-ligand binding affinity prediction (BAP), providing a fresh perspective on this evolving field.
Methods: We thoroughly examine commonly used datasets for BAP and their inherent characteristics. Our exploration extends to various preprocessing steps and DL techniques, including graph neural networks, convolutional neural networks, and transformers, which are found in the literature. We conducted extensive literature research to ensure that the most recent deep learning approaches for BAP were included by the time of writing this manuscript.
Results: The systematic approach used for the present study highlighted inherent challenges to BAP via DL, such as data quality, model interpretability, and explainability, and proposed considerations for future research directions. We present valuable insights to accelerate the development of more effective and reliable DL models for BAP within the research community.
Conclusion: The present study can considerably enhance future research on predicting affinity between protein and ligand molecules, hence further improving the overall drug development process.
{"title":"Advances in Protein-Ligand Binding Affinity Prediction via Deep Learning: A Comprehensive Study of Datasets, Data Preprocessing Techniques, and Model Architectures.","authors":"Gelany Aly Abdelkader, Jeong-Dong Kim","doi":"10.2174/0113894501330963240905083020","DOIUrl":"10.2174/0113894501330963240905083020","url":null,"abstract":"<p><strong>Background: </strong>Drug discovery is a complex and expensive procedure involving several timely and costly phases through which new potential pharmaceutical compounds must pass to get approved. One of these critical steps is the identification and optimization of lead compounds, which has been made more accessible by the introduction of computational methods, including deep learning (DL) techniques. Diverse DL model architectures have been put forward to learn the vast landscape of interaction between proteins and ligands and predict their affinity, helping in the identification of lead compounds.</p><p><strong>Objective: </strong>This survey fills a gap in previous research by comprehensively analyzing the most commonly used datasets and discussing their quality and limitations. It also offers a comprehensive classification of the most recent DL methods in the context of protein-ligand binding affinity prediction (BAP), providing a fresh perspective on this evolving field.</p><p><strong>Methods: </strong>We thoroughly examine commonly used datasets for BAP and their inherent characteristics. Our exploration extends to various preprocessing steps and DL techniques, including graph neural networks, convolutional neural networks, and transformers, which are found in the literature. We conducted extensive literature research to ensure that the most recent deep learning approaches for BAP were included by the time of writing this manuscript.</p><p><strong>Results: </strong>The systematic approach used for the present study highlighted inherent challenges to BAP via DL, such as data quality, model interpretability, and explainability, and proposed considerations for future research directions. We present valuable insights to accelerate the development of more effective and reliable DL models for BAP within the research community.</p><p><strong>Conclusion: </strong>The present study can considerably enhance future research on predicting affinity between protein and ligand molecules, hence further improving the overall drug development process.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.2174/0113894501323529240910015912
Mohammad Amin Habibi, Sajjad Ahmadpour, Javad Tafaroji, Seyed Mohammad Eazi, Pooryia Mineaie, Yousef Mohammadpour, Soheil Tavakolpour
Remission failure and relapse numerate as one of the main problems in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAVs). The need for new agents that provide effective and safe induction accompanied by sustained remission seems to be urgent in clinical care. The efficacy and safety of rituximab (RTX) for AAVs therapy has been reported in various studies. RTX therapy offers several advantages to treating AAVs patients compared to other therapeutic approaches including reduction of Glucocorticoids (GCs) and conventional Immunosuppressive therapy (IST) usage during both the induction of remission and maintenance phases. This reduction can lead to a lower rate of serious complications making RTX therapy a safer option. It seems that RTX may provide improved clinical outcomes in these patients mediated via B-lymphocyte depletion, Proteinase 3-antineutrophilic cytoplasmic antibody (PR3-ANCA), and myeloperoxidase-antineutrophilic cytoplasmic antibody (MPO-ANCA) titers reduction. In this regard, some uncertainties have been reported to validate the association between such depletion and clinical improvement, as suggested by other sources of autoreactive B cells that did not target with RTX. Due to the prolonged B cell depletion, fixed intervals and adjusted dosage of RTX may be required in patients with AAVs. In this narrative review, we aimed to insight better understand regarding the efficacy of RTX for effective induction and sustained remission in patients with AAVs. It seems that discovering new biomarkers predicting relapse in AAVs patients can lead to future targeted therapy.
缓解失败和复发是抗中性粒细胞胞浆抗体相关性血管炎(AAVs)患者面临的主要问题之一。临床治疗急需新的药物,以提供有效、安全的诱导和持续缓解。已有多项研究报道了利妥昔单抗(RTX)治疗 AAVs 的有效性和安全性。与其他治疗方法相比,RTX疗法在治疗AAVs患者方面具有多项优势,包括在诱导缓解和维持治疗阶段减少糖皮质激素(GCs)和传统免疫抑制剂(IST)的使用。这种减少可降低严重并发症的发生率,使 RTX 疗法成为更安全的选择。RTX似乎可以通过B淋巴细胞耗竭、蛋白酶3-抗中性粒细胞胞浆抗体(PR3-ANCA)和髓过氧化物酶-抗中性粒细胞胞浆抗体(MPO-ANCA)滴度降低来改善这些患者的临床疗效。在这方面,有报告称,由于其他来源的自反应性 B 细胞并不是 RTX 的靶点,因此在验证这种耗竭与临床改善之间的联系时存在一些不确定性。由于 B 细胞耗竭时间较长,AAV 患者可能需要固定的 RTX 间隔和调整剂量。在这篇叙述性综述中,我们旨在深入了解RTX对AAV患者有效诱导和持续缓解的疗效。发现预测AAVs患者复发的新生物标志物似乎可以为未来的靶向治疗提供依据。
{"title":"Two Decades Rituximab Therapy in Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis.","authors":"Mohammad Amin Habibi, Sajjad Ahmadpour, Javad Tafaroji, Seyed Mohammad Eazi, Pooryia Mineaie, Yousef Mohammadpour, Soheil Tavakolpour","doi":"10.2174/0113894501323529240910015912","DOIUrl":"https://doi.org/10.2174/0113894501323529240910015912","url":null,"abstract":"<p><p>Remission failure and relapse numerate as one of the main problems in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAVs). The need for new agents that provide effective and safe induction accompanied by sustained remission seems to be urgent in clinical care. The efficacy and safety of rituximab (RTX) for AAVs therapy has been reported in various studies. RTX therapy offers several advantages to treating AAVs patients compared to other therapeutic approaches including reduction of Glucocorticoids (GCs) and conventional Immunosuppressive therapy (IST) usage during both the induction of remission and maintenance phases. This reduction can lead to a lower rate of serious complications making RTX therapy a safer option. It seems that RTX may provide improved clinical outcomes in these patients mediated via B-lymphocyte depletion, Proteinase 3-antineutrophilic cytoplasmic antibody (PR3-ANCA), and myeloperoxidase-antineutrophilic cytoplasmic antibody (MPO-ANCA) titers reduction. In this regard, some uncertainties have been reported to validate the association between such depletion and clinical improvement, as suggested by other sources of autoreactive B cells that did not target with RTX. Due to the prolonged B cell depletion, fixed intervals and adjusted dosage of RTX may be required in patients with AAVs. In this narrative review, we aimed to insight better understand regarding the efficacy of RTX for effective induction and sustained remission in patients with AAVs. It seems that discovering new biomarkers predicting relapse in AAVs patients can lead to future targeted therapy.</p>","PeriodicalId":10805,"journal":{"name":"Current drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}