Medicine in Drug Discovery最新文献

英文中文

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-01-01

引用次数: 0

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-01-01

引用次数: 0

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-01-01

引用次数: 0

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2025-01-01

引用次数: 0

The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain 视网膜下素/视黄醛受体 mRNA 在小鼠和人脑中的分布

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2024-10-10 DOI: 10.1016/j.medidd.2024.100202

Sanjida Mir , Ryan J. Keenan , Romke Bron , Cameron J. Nowell , Catriona McLean , Leah C. Beauchamp , Laura J. Vella , Brian Dean , Daniel Hoyer , Laura H. Jacobson

Hypocretin (Hcrtr, HCRTR) / orexin (OX) receptors modulate a range of neurobiological functions and are drug targets for several disorders. Mapping the distribution of receptors in the brain can inform their function and guide targeting of specific disorders. Although studied in rodents, orexin receptor distribution has remained relatively unexplored in humans, and thus there is also a paucity of comparative anatomy. The aim of this study was therefore to map the distribution of hypocretin/orexin receptor mRNA in selected regions of the mouse and human brain by non-radioactive in situ hybridization (ISH) using digoxigenin (DIG)-labelled cRNA anti-sense probes. Data revealed both distinct and overlapping patterns of distributions of Hcrtr1/HCRTR1 and Hcrtr2/HCRTR2 mRNA suggesting that the functions of the orexin system are mediated differently by each receptor. In the mouse brain, the highest expression of Hcrtr1 mRNA was in the locus coeruleus (LC) whereas Hcrtr2 mRNA was most abundant in the lateral hypothalamus (LH). The human caudate nuclei showed significant expression of both HCRTR1 and HCRTR2 mRNA, whereas the mouse predominantly expressed Hcrtr2 mRNA. The noradrenergic neurons of the human LC showed high signals for both HCRTR1 (71.7%) and HCRTR2 (81.5%) mRNA. Expression of HCRTR2 mRNA in non-noradrenergic human LC cells was also notable. The distribution pattern in mouse and human brains is consistent with the involvement of the orexin system in arousal and the sleep/wake cycle in both species, however, variations in receptor subtype expression profiles suggests that species differences in responses to orexin receptor ligands may be expected.

视网膜下素（Hcrtr，HCRTR）/奥曲肽受体（OX）可调节一系列神经生物学功能，是治疗多种疾病的药物靶点。绘制受体在大脑中的分布图可以了解受体的功能，并指导针对特定疾病的治疗。虽然在啮齿类动物中对奥曲肽受体的分布进行了研究，但在人类中的研究相对较少，因此也缺乏比较解剖学研究。因此，本研究的目的是利用地高辛（DIG）标记的 cRNA 反义探针，通过非放射性原位杂交（ISH）绘制小鼠和人类大脑选定区域的视网膜下素/奥曲肽受体 mRNA 分布图。数据显示，Hcrtr1/HCRTR1和Hcrtr2/HCRTR2 mRNA的分布既有区别又有重叠，这表明奥曲肽系统的功能是由每种受体以不同方式介导的。在小鼠大脑中，Hcrtr1 mRNA 的最高表达量在脑室（LC），而 Hcrtr2 mRNA 在下丘脑外侧（LH）的表达量最高。人类尾状核显示 HCRTR1 和 HCRTR2 mRNA 均有显著表达，而小鼠则主要表达 Hcrtr2 mRNA。人LC的去甲肾上腺素能神经元的HCRTR1（71.7%）和HCRTR2（81.5%）mRNA均显示高信号。在非去甲肾上腺素能的人 LC 细胞中，HCRTR2 mRNA 的表达也很显著。小鼠和人脑中的分布模式与奥曲肽系统参与两种动物的唤醒和睡眠/觉醒周期是一致的，但是，受体亚型表达谱的差异表明，物种对奥曲肽受体配体的反应可能存在差异。

{"title":"The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain","authors":"Sanjida Mir , Ryan J. Keenan , Romke Bron , Cameron J. Nowell , Catriona McLean , Leah C. Beauchamp , Laura J. Vella , Brian Dean , Daniel Hoyer , Laura H. Jacobson","doi":"10.1016/j.medidd.2024.100202","DOIUrl":"10.1016/j.medidd.2024.100202","url":null,"abstract":"<div><div>Hypocretin (<em>Hcrtr, HCRTR</em>) / orexin (OX) receptors modulate a range of neurobiological functions and are drug targets for several disorders. Mapping the distribution of receptors in the brain can inform their function and guide targeting of specific disorders. Although studied in rodents, orexin receptor distribution has remained relatively unexplored in humans, and thus there is also a paucity of comparative anatomy. The aim of this study was therefore to map the distribution of hypocretin/orexin receptor mRNA in selected regions of the mouse and human brain by non-radioactive in situ hybridization (ISH) using digoxigenin (DIG)-labelled cRNA anti-sense probes. Data revealed both distinct and overlapping patterns of distributions of <em>Hcrtr1/HCRTR1</em> and <em>Hcrtr2/HCRTR2</em> mRNA suggesting that the functions of the orexin system are mediated differently by each receptor. In the mouse brain, the highest expression of <em>Hcrtr1</em> mRNA was in the locus coeruleus (LC) whereas <em>Hcrtr2</em> mRNA was most abundant in the lateral hypothalamus (LH). The human caudate nuclei showed significant expression of both <em>HCRTR1</em> and <em>HCRTR2</em> mRNA, whereas the mouse predominantly expressed <em>Hcrtr2</em> mRNA. The noradrenergic neurons of the human LC showed high signals for both <em>HCRTR1</em> (71.7%) and <em>HCRTR2</em> (81.5%) mRNA. Expression of <em>HCRTR2</em> mRNA in non-noradrenergic human LC cells was also notable. The distribution pattern in mouse and human brains is consistent with the involvement of the orexin system in arousal and the sleep/wake cycle in both species, however, variations in receptor subtype expression profiles suggests that species differences in responses to orexin receptor ligands may be expected.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural features of arrestin-mediated GPCR signaling 捕获素介导的 GPCR 信号的结构特征

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2024-10-10 DOI: 10.1016/j.medidd.2024.100201

Wenqin Xie , Jinglin Lai , Hongmin Cai , H. Eric Xu , Wanchao Yin

G protein-coupled receptors (GPCRs) constitute a diverse and extensive array of cell surface receptors, rendering them essential targets for drugs aimed at various human diseases. Responding to a range of extracellular or intracellular cues, GPCRs regulate cellular signaling through downstream transducers such as heterotrimer G proteins, GPCR kinases (GRKs), and arrestins. The wealth of 3D structures available for GPCRs and their signaling complexes significantly enhances our understanding of GPCR biology and expedites the development of structure-based drug discovery methods aimed at GPCR signaling. While the structural exploration of GPCR-G protein complexes has advanced, recent years have seen substantial breakthroughs in unraveling the mechanism behind arrestin-mediated GPCR signaling. This review aims to explore emerging insights into arrestin activation and its interaction with GPCRs, shedding light on the various ways GPCRs engage with arrestins both conservatively and diversely. Additionally, we summarize recent endeavors focused on designing functionally selective (’biased’) ligands targeting GPCRs, with desired effects on/off arrestin signaling. Our goal with this review is to spotlight studies investigating the structural aspects of GPCR activation and arrestin-binding modes, with a specific emphasis on arrestin-mediated GPCR signaling.

G 蛋白偶联受体（GPCR）构成了多种多样的细胞表面受体，使它们成为治疗各种人类疾病药物的重要靶点。GPCR 可对一系列细胞外或细胞内线索做出反应，并通过异三聚 G 蛋白、GPCR 激酶 (GRK) 和抑制素等下游传导因子调节细胞信号传导。大量 GPCR 及其信号复合物的三维结构大大增强了我们对 GPCR 生物学的了解，并加快了针对 GPCR 信号转导的基于结构的药物发现方法的开发。在对 GPCR-G 蛋白复合物进行结构探索的同时，近年来在揭示 arrestin 介导的 GPCR 信号转导机制方面也取得了重大突破。这篇综述旨在探讨关于捕获素激活及其与 GPCR 相互作用的新见解，揭示 GPCR 与捕获素保守和多样化接触的各种方式。此外，我们还总结了最近在设计针对 GPCR 的功能选择性（"偏向性"）配体方面所做的努力，这些配体对/对 arrestin 信号转导具有理想的效果。我们撰写这篇综述的目的是重点介绍有关 GPCR 激活和 arrestin 结合模式的结构方面的研究，并特别强调 arrestin 介导的 GPCR 信号转导。

{"title":"Structural features of arrestin-mediated GPCR signaling","authors":"Wenqin Xie , Jinglin Lai , Hongmin Cai , H. Eric Xu , Wanchao Yin","doi":"10.1016/j.medidd.2024.100201","DOIUrl":"10.1016/j.medidd.2024.100201","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) constitute a diverse and extensive array of cell surface receptors, rendering them essential targets for drugs aimed at various human diseases. Responding to a range of extracellular or intracellular cues, GPCRs regulate cellular signaling through downstream transducers such as heterotrimer G proteins, GPCR kinases (GRKs), and arrestins. The wealth of 3D structures available for GPCRs and their signaling complexes significantly enhances our understanding of GPCR biology and expedites the development of structure-based drug discovery methods aimed at GPCR signaling. While the structural exploration of GPCR-G protein complexes has advanced, recent years have seen substantial breakthroughs in unraveling the mechanism behind arrestin-mediated GPCR signaling. This review aims to explore emerging insights into arrestin activation and its interaction with GPCRs, shedding light on the various ways GPCRs engage with arrestins both conservatively and diversely. Additionally, we summarize recent endeavors focused on designing functionally selective (’biased’) ligands targeting GPCRs, with desired effects on/off arrestin signaling. Our goal with this review is to spotlight studies investigating the structural aspects of GPCR activation and arrestin-binding modes, with a specific emphasis on arrestin-mediated GPCR signaling.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100201"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting BCL-2 family proteins using BH3 mimetic drugs for cancer therapy: A systematic review of randomized clinical trials 使用 BH3 拟态药物靶向 BCL-2 家族蛋白治疗癌症：随机临床试验系统回顾

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2024-09-29 DOI: 10.1016/j.medidd.2024.100199

Fatimah Alharbi, Eyad Almanifi, Md. Ashrafuzzaman

Apoptosis plays a significant role in both carcinogenesis and cancer treatment. Apoptotic dysfunction may allow cancer cells to survive. Overexpression of anti-apoptotic B cell lymphoma-2 (BCL-2) family protein members is predicted to majorly contribute to apoptotic dysfunction. Therefore, targeting proteins in cancer has been of interest to scientists and drug developers. The most successful method to regulate apoptosis in cancer cells so far has been found in the development of BH3-mimetic drugs that may work towards downregulating anti-apoptotic BCL-2 protein functions. Clinical trials have dealt with a few molecules that mimic the function of BH3-only proteins and therefore inhibit their anti-apoptotic functions. Currently, this approach is one of the most promising and effective strategies for cancer treatment. Since the family has more than fifteen protein members, this review will focus on three members that have garnered interest as therapeutic targets: Bcl-2, Bcl-X_L, and myeloid cell leukaemia 1 (Mcl-1), all are anti-apoptosis proteins. In addition, it covers the major functions of Bcl-2, Bcl-X_L, and MCL-1, their implication in malignancy, as well as their pharmacologic inhibitors. The Food and Drug Administration has approved the first BH-3 mimetic, venetoclax, an oral Bcl-2 inhibitor shown to treat chronic lymphocytic leukemia. This systematic review of clinical trials investigates the efficacy and clinical relevance of BCL-2 family protein inhibitors in managing malignancies.

细胞凋亡在致癌和癌症治疗中都发挥着重要作用。凋亡功能障碍可能使癌细胞得以存活。据预测，抗凋亡 B 细胞淋巴瘤-2（BCL-2）家族蛋白成员的过度表达是导致细胞凋亡功能障碍的主要原因。因此，针对癌症蛋白的研究一直备受科学家和药物开发人员的关注。迄今为止，调控癌细胞凋亡最成功的方法是开发 BH3 拟态药物，这些药物可以下调抗凋亡 BCL-2 蛋白的功能。临床试验已经涉及了一些分子，这些分子可模仿纯 BH3 蛋白的功能，从而抑制其抗凋亡功能。目前，这种方法是最有前途和最有效的癌症治疗策略之一。由于该家族有超过 15 个蛋白成员，本综述将重点介绍其中作为治疗靶点而备受关注的三个成员：Bcl-2、Bcl-XL 和骨髓细胞白血病 1（Mcl-1）都是抗凋亡蛋白。此外，该书还介绍了 Bcl-2、Bcl-XL 和 MCL-1 的主要功能、它们在恶性肿瘤中的作用以及它们的药物抑制剂。美国食品和药物管理局已经批准了第一种 BH-3 拟效药 venetoclax，这是一种口服 Bcl-2 抑制剂，可用于治疗慢性淋巴细胞白血病。这篇临床试验系统综述探讨了BCL-2家族蛋白抑制剂在治疗恶性肿瘤方面的疗效和临床意义。

{"title":"Targeting BCL-2 family proteins using BH3 mimetic drugs for cancer therapy: A systematic review of randomized clinical trials","authors":"Fatimah Alharbi, Eyad Almanifi, Md. Ashrafuzzaman","doi":"10.1016/j.medidd.2024.100199","DOIUrl":"10.1016/j.medidd.2024.100199","url":null,"abstract":"<div><div>Apoptosis plays a significant role in both carcinogenesis and cancer treatment. Apoptotic dysfunction may allow cancer cells to survive. Overexpression of anti-apoptotic B cell lymphoma-2 (BCL-2) family protein members is predicted to majorly contribute to apoptotic dysfunction. Therefore, targeting proteins in cancer has been of interest to scientists and drug developers. The most successful method to regulate apoptosis in cancer cells so far has been found in the development of BH3-mimetic drugs that may work towards downregulating anti-apoptotic BCL-2 protein functions. Clinical trials have dealt with a few molecules that mimic the function of BH3-only proteins and therefore inhibit their anti-apoptotic functions. Currently, this approach is one of the most promising and effective strategies for cancer treatment. Since the family has more than fifteen protein members, this review will focus on three members that have garnered interest as therapeutic targets: Bcl-2, Bcl-X<sub>L</sub>, and myeloid cell leukaemia 1 (Mcl-1), all are anti-apoptosis proteins. In addition, it covers the major functions of Bcl-2, Bcl-X<sub>L</sub>, and MCL-1, their implication in malignancy, as well as their pharmacologic inhibitors. The Food and Drug Administration has approved the first BH-3 mimetic, venetoclax, an oral Bcl-2 inhibitor shown to treat chronic lymphocytic leukemia. This systematic review of clinical trials investigates the efficacy and clinical relevance of BCL-2 family protein inhibitors in managing malignancies.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacological effects of dragon’s blood from Dranaena cochinchinensis (Lour.) S.C. Chen and its application in cardiovascular diseases 陈氏龙血的药理作用及其在心血管疾病中的应用

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2024-09-27 DOI: 10.1016/j.medidd.2024.100200

Hui-juan Zhang , Kai-xuan Lin , Li-dan Fu , Francis Chanda , Abdallah Iddy Chaurembo , Jian-yuan Huang , Yun-jing Xu , Chi Shu , Ke Yang , Na Xing , Wei-bo Dai , Han-bin Lin

Dragon’s blood (Resina Draconis) is the red resin of Dracaena spp, which has a variety of biological activities and pharmacological effects, including anti-thrombotic, anti-inflammatory, anti-bacterial, analgesic, anti-oxidant, anti-tumor, and immunosuppressive. In China, the main source of dragon’s blood is Dranaena Cochinchinensis (Lour.) S.C.Chen. A wide array of studies have speculated that the dragon’s blood derived from Dranaena Cochinchinensis (Lour.) S.C.Chen possesses cardiovascular protective effects. It has been reported that Chinese dragon’s blood can potentially alleviate and treat conditions such as coronary heart disease, myocardial infarction, and myocardial ischemia–reperfusion through its anti-inflammatory and antioxidant properties, which have not been systematically stated in previous reviews. Moreover, the precise underlying pharmacological mechanisms through which the Chinese dragon’s blood exhibits cardioprotective effects are not fully understood. Therefore, this article discusses the pharmacological action and biomolecular mechanism of dragon’s blood from Dranaena Cochinchinensis (Lour.) S.C.Chen and how it prevents and protects against cardiovascular diseases. The review article concludes with prospects for further application of dragon’s blood in respect to cardiovascular diseases.

龙血树（Resina Draconis）是龙血树属植物的红色树脂，具有抗血栓、抗炎、抗菌、镇痛、抗氧化、抗肿瘤、免疫抑制等多种生物活性和药理作用。在中国，龙血树的主要产地是陈氏龙血树（Dranaena Cochinchinensis (Lour.) S.C.Chen）。大量研究推测，从陈皮中提取的龙血具有保护心血管的作用。据报道，中国龙血可通过其抗炎和抗氧化特性，缓解和治疗冠心病、心肌梗塞和心肌缺血再灌注等疾病，但在以往的综述中尚未系统地阐述这些特性。此外，中国龙血具有心脏保护作用的确切药理机制尚未完全清楚。因此，本文探讨了陈氏龙血的药理作用和生物分子机制，以及它如何预防和保护心血管疾病。综述文章最后对龙血在心血管疾病方面的进一步应用进行了展望。

{"title":"Pharmacological effects of dragon’s blood from Dranaena cochinchinensis (Lour.) S.C. Chen and its application in cardiovascular diseases","authors":"Hui-juan Zhang , Kai-xuan Lin , Li-dan Fu , Francis Chanda , Abdallah Iddy Chaurembo , Jian-yuan Huang , Yun-jing Xu , Chi Shu , Ke Yang , Na Xing , Wei-bo Dai , Han-bin Lin","doi":"10.1016/j.medidd.2024.100200","DOIUrl":"10.1016/j.medidd.2024.100200","url":null,"abstract":"<div><div>Dragon’s blood (<em>Resina Draconis</em>) is the red resin of <em>Dracaena</em> spp, which has a variety of biological activities and pharmacological effects, including anti-thrombotic, anti-inflammatory, anti-bacterial, analgesic, anti-oxidant, anti-tumor, and immunosuppressive. In China, the main source of dragon’s blood is <em>Dranaena Cochinchinensis</em> (Lour.) S.C.Chen. A wide array of studies have speculated that the dragon’s blood derived from <em>Dranaena Cochinchinensis</em> (Lour.) S.C.Chen possesses cardiovascular protective effects. It has been reported that Chinese dragon’s blood can potentially alleviate and treat conditions such as coronary heart disease, myocardial infarction, and myocardial ischemia–reperfusion through its anti-inflammatory and antioxidant properties, which have not been systematically stated in previous reviews. Moreover, the precise underlying pharmacological mechanisms through which the Chinese dragon’s blood exhibits cardioprotective effects are not fully understood. Therefore, this article discusses the pharmacological action and biomolecular mechanism of dragon’s blood from <em>Dranaena Cochinchinensis</em> (Lour.) S.C.Chen and how it prevents and protects against cardiovascular diseases. The review article concludes with prospects for further application of dragon’s blood in respect to cardiovascular diseases.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coronavirus spike protein-based vaccines. Vaccine delivery systems 冠状病毒尖峰蛋白疫苗。疫苗输送系统

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2024-09-12 DOI: 10.1016/j.medidd.2024.100198

Akmal M. Asrorov , Mirzakamol S. Ayubov , Bin Tu , Mingjie Shi , Huiyuan Wang , Sharafitdin Mirzaakhmedov , Amit Kumar Nayak , Ibrokhim Y. Abdurakhmonov , Yongzhuo Huang

Spike protein has been established as one of the molecules playing a pivotal role in coronavirus infection. On its bases, several vaccines have been developed, passed preclinical and clinical stages, and reached medical practice at the early stages of the pandemic. It was found efficient enough to induce various types of immunoglobulins. However, the missense mutations made it necessary to develop new sequences with adjuvants to enhance the efficacy against a broad spectrum of SARS-CoV-2 and newly emerging variants. Some attempts were carried out to improve the vaccine efficiency by loading it into a delivery system, which caused a prolongation effect. In this paper, we reviewed data around spike protein-based vaccines in terms of their efficacy, which was analyzed based on enhanced quantities/titers of immunoglobulins/neutralizing antibodies. Our search on the PubMed database using ‘spike protein-based coronavirus vaccines’ keywords showed over 150 publications that were further filtered based on their relevance. Further, we added other relevant papers to support the expressed ideas. We compared the effects of various vaccines of different origins in clinical studies and animal experiments where relevant. The efficacy of adjuvants has been reviewed as a separate section. In several cases, we explained the significance of the spike protein trimeric structure. We also explained the essential role of mutation while developing protein vaccines. The contributions of adjuvants in inducing immune responses have been separated into one section. The outcomes of clinical studies were highlighted to prove their efficacies.

穗状病毒蛋白已被确定为在冠状病毒感染中起关键作用的分子之一。在它的基础上开发了几种疫苗，通过了临床前和临床阶段，并在大流行的早期阶段进入了医疗实践。人们发现它能有效诱导各种类型的免疫球蛋白。然而，由于存在错义突变，有必要开发新的序列和佐剂，以提高对 SARS-CoV-2 和新出现的变种的广谱效力。有人尝试通过将疫苗装入输送系统来提高疫苗的效率，但这样做会导致疫苗效期延长。在本文中，我们回顾了以尖峰蛋白为基础的疫苗的疗效数据，这些数据是根据免疫球蛋白/中和抗体的增强量/滴度进行分析的。我们使用 "基于尖峰蛋白的冠状病毒疫苗 "关键词在 PubMed 数据库中进行了搜索，结果显示有 150 多篇论文，我们根据这些论文的相关性对其进行了进一步筛选。此外，我们还添加了其他相关论文以支持所表达的观点。我们比较了不同来源的各种疫苗在临床研究和相关动物实验中的效果。佐剂的功效作为一个单独的部分进行了综述。在多个案例中，我们解释了尖峰蛋白三聚体结构的重要性。我们还解释了突变在开发蛋白质疫苗中的重要作用。佐剂在诱导免疫反应中的作用被单独列为一节。我们还重点介绍了临床研究的成果，以证明它们的功效。

{"title":"Coronavirus spike protein-based vaccines. Vaccine delivery systems","authors":"Akmal M. Asrorov , Mirzakamol S. Ayubov , Bin Tu , Mingjie Shi , Huiyuan Wang , Sharafitdin Mirzaakhmedov , Amit Kumar Nayak , Ibrokhim Y. Abdurakhmonov , Yongzhuo Huang","doi":"10.1016/j.medidd.2024.100198","DOIUrl":"10.1016/j.medidd.2024.100198","url":null,"abstract":"<div><p>Spike protein has been established as one of the molecules playing a pivotal role in coronavirus infection. On its bases, several vaccines have been developed, passed preclinical and clinical stages, and reached medical practice at the early stages of the pandemic. It was found efficient enough to induce various types of immunoglobulins. However, the missense mutations made it necessary to develop new sequences with adjuvants to enhance the efficacy against a broad spectrum of SARS-CoV-2 and newly emerging variants. Some attempts were carried out to improve the vaccine efficiency by loading it into a delivery system, which caused a prolongation effect. In this paper, we reviewed data around spike protein-based vaccines in terms of their efficacy, which was analyzed based on enhanced quantities/titers of immunoglobulins/neutralizing antibodies. Our search on the PubMed database using ‘spike protein-based coronavirus vaccines’ keywords showed over 150 publications that were further filtered based on their relevance. Further, we added other relevant papers to support the expressed ideas. We compared the effects of various vaccines of different origins in clinical studies and animal experiments where relevant. The efficacy of adjuvants has been reviewed as a separate section. In several cases, we explained the significance of the spike protein trimeric structure. We also explained the essential role of mutation while developing protein vaccines. The contributions of adjuvants in inducing immune responses have been separated into one section. The outcomes of clinical studies were highlighted to prove their efficacies.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259009862400023X/pdfft?md5=1848354a80eb802b2c91988187479acd&pid=1-s2.0-S259009862400023X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unlocking the therapeutic capabilities of GPCR in the treatment of ischemic stroke: A translational literature 释放 GPCR 在治疗缺血性中风方面的治疗能力：转化文献

Q2 Medicine

Medicine in Drug Discovery

Pub Date : 2024-08-22 DOI: 10.1016/j.medidd.2024.100197

Girish B S Pharm.D, Nikitha B S Pharm.D, Roopa K Pharm.D, Meghana C S Pharm.D, Srinivasan R M.Pharm, PhD

GPCRs are a class of membrane proteins that are essential to signal transduction, and this is a vital process in many different physiologies. The significant mortality rate and widespread occurrence of stroke highlight the need to accelerate the research to develop viable treatment agents. A promising prospect for the development of new treatment approaches is the increasing comprehension of the pathophysiology of stroke and the crucial roles played by GPCRs. Because of the blood clot, the glial cells’ vascular supply is abruptly cut off, which sets off a series of events that include inflammation and neuronal damage and ultimately lead to cell death. Numerous therapeutic treatments, including thrombolytic agents like tissue plasminogen activator and urokinase, have been discovered as potential neuroprotective medicines; however, their use is restricted because of the modest therapeutic window. Accepting that GPCRs are the pertinent factors in ischemic stroke, we explore the potential medicinal promise of GPCR-targeted treatments and the shortcomings that ought to be resolved in order to translate these discoveries to clinical cases.

GPCR 是一类对信号转导至关重要的膜蛋白，是许多不同生理机能中的重要过程。中风死亡率高，发病范围广，因此需要加快研究，开发可行的治疗药物。对中风病理生理学和 GPCRs 关键作用的理解不断加深，为开发新的治疗方法带来了广阔的前景。由于血凝块的存在，神经胶质细胞的血管供应突然中断，引发了一系列事件，包括炎症和神经元损伤，最终导致细胞死亡。目前已经发现了许多潜在的神经保护药物，包括组织纤溶酶原激活剂和尿激酶等溶栓药物，但由于治疗窗口期较短，这些药物的使用受到了限制。鉴于 GPCR 是缺血性中风的相关因素，我们探讨了 GPCR 靶向治疗的潜在药用前景，以及将这些发现转化为临床病例需要解决的不足之处。

{"title":"Unlocking the therapeutic capabilities of GPCR in the treatment of ischemic stroke: A translational literature","authors":"Girish B S Pharm.D, Nikitha B S Pharm.D, Roopa K Pharm.D, Meghana C S Pharm.D, Srinivasan R M.Pharm, PhD","doi":"10.1016/j.medidd.2024.100197","DOIUrl":"10.1016/j.medidd.2024.100197","url":null,"abstract":"<div><p>GPCRs are a class of membrane proteins that are essential to signal transduction, and this is a vital process in many different physiologies. The significant mortality rate and widespread occurrence of stroke highlight the need to accelerate the research to develop viable treatment agents. A promising prospect for the development of new treatment approaches is the increasing comprehension of the pathophysiology of stroke and the crucial roles played by GPCRs. Because of the blood clot, the glial cells’ vascular supply is abruptly cut off, which sets off a series of events that include inflammation and neuronal damage and ultimately lead to cell death. Numerous therapeutic treatments, including thrombolytic agents like tissue plasminogen activator and urokinase, have been discovered as potential neuroprotective medicines; however, their use is restricted because of the modest therapeutic window. Accepting that GPCRs are the pertinent factors in ischemic stroke, we explore the potential medicinal promise of GPCR-targeted treatments and the shortcomings that ought to be resolved in order to translate these discoveries to clinical cases.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"24 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000228/pdfft?md5=7ea1babb292d6f267fc89fefc770927a&pid=1-s2.0-S2590098624000228-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

首页上一页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Medicine in Drug Discovery

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀